vertical gaze palsy

7/24/2019 Vertical Gaze Palsy

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11/08/14 ertical gaze palsy

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Vertical gaze palsyContributors

Heather E Moss MDPhD, author. Dr. Moss of the University of Illinois at Chicagohas no relevant financial relationships to disclose.

James Goodwin MD, editor. Dr. Goodwin of the University of Illinois at Chicagohas no relevant financial relationships to disclose.

Former author(s)

Jason J S Barton MD PhD

Publication dates

Originally released July 19, 2001; last updated March 5, 2014; expires March 5,2017

SynonymsGaze paresis; Gaze preference; Saccadic palsy

Key points Vertical gaze palsies are due to damage to pre-motor structures in themidbrain, namely the rostral interstitial nucleus of the medial longitudinalfasciculus and the interstitial nuclear of Cajal. Vertical gaze palsies can involve upgaze, downgaze, or both. Parkinsonian conditions with vertical gaze palsies are due most often totauopathies, such as progressive supranuclear palsyand corticobasaldegeneration. Several genetic defects can cause cerebellar ataxiawith vertical gaze palsies,chief of which is Niemann Pick type C disease.

Historical note and nomenclature The term gaze palsy is best restricted to deficits in conjugate eye movementsthat affect both eyes. Thus, strictly unilateral problems such as palsiesof cranialnerves III, IV, or VI are not gaze palsies, even though they do affect gaze.Likewise, impairments in vergence control, such as convergence or divergenceinsufficiency, are not gaze palsies, as they do not involve conjugate eyemovements. A fundamental distinction is between vertical and horizontal gaze palsies. Most

gaze palsies affect 1 direction in 1 plane of eye movement only, reflecting theseparation of the prenuclear control systems for vertical and horizontal eyemovement. Reduction of eye movements in all planes is best termedgeneralized ophthalmoparesis. These reductions are most commonlymyopathic, occurring with mitochondrial disorders(chronic progressive externalophthalmoplegia, Kearns-Sayre syndrome, MELAS), muscular dystrophies(myotonic dystrophy, oculopharyngeal dystrophy, congenital fibrosis),myasthenia gravis, or thyroid eye disease, among others. The term gaze palsy requires further elaboration. There are many differenttypes of conjugate eye movements, including saccades, pursuit, optokinetic, and

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Illustrations

- Enhancing pretectal lesicausing Parinaud syndro(sagittal MRI)

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- Vertical gaze palsy (axiaMRI)

Diagrams- Ocular motor control

structures in brainstem(sagittal drawing)

Videos

- Niemann Pick type C: eymovements

- Parkinsonism and upgazpalsy (posttraumatic)treated with shunting

- Progressive supranuclea
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vestibulo-ocular responses. The anatomic systems that control these diverge andconverge at various levels, and it is possible for some lesions to impair some eyemovement systems and spare others. Hence, a left saccadic palsyis a selectivegaze palsy affecting only leftward saccades but not leftward pursuit or vestibulo-ocular response. A palsy affecting all types of eye movements should bedesignated as a nonselective gaze palsy. Most vertical gaze palsies are selectivein nature. In contrast, the terms partial or complete when applied to gaze palsy

indicate whether some motion across midline in the paretic direction is present.

Clinical manifestations Vertical palsies usually appear selective, affecting primarily saccades. However,though clinical testing often shows sparing of pursuit and vestibulo-ocular range,quantitative testing of eye movements shows that this selectivity is relative andnot absolute (Sharpe and Kim 2002). Pursuit gain and vestibulo-ocular reflexesare impaired in many patients, though dissociable. Upgaze palsy is mostfrequent, combined upgaze and downgaze palsy is next in frequency, and puredowngaze palsy the most unusual (Bogousslavsky et al 1988). Because these aredue to lesions of rostral midbrain nuclei, associated signs include pupillary or

ocular motor signs of partial nuclear or fascicular third palsies (Castaigne et al1981;Beversdorff et al 1995), including rarely a wall-eyed bilateral internuclearophthalmoplegia(Sierra-Hidalgo et al 2010), impaired convergence, and skewdeviation (Ranalli and Sharpe 1988;Steinke et al 1992). Somnolence or even atransient fluctuating comaat onset reflects damage to the reticular activatingsystem (Castaigne et al 1981;Bogousslavsky et al 1988;Beversdorff et al1995). Behavioral disturbances from thalamic damage include hemineglect,amnestic syndromes (Bogousslavsky et al 1988;Beversdorff et al 1995), akineticmutism, or subcortical demented states with apathy and slowness of thought(Guberman and Stuss 1983). Upgaze palsy. This is frequent with unilateral lesions at either thethalamomesencephalic junction (Bogousslavsky et al 1986;1988), or the

posterior commissure, or its nucleus (Buttner-Ennever et al 1982). There areoften other signs of the pretectal syndrome. A lesion of the periaqueductal greymatter rarely causes this, perhaps by destroying descending outputs from theriMLF(Thames et al 1984). Rarely, it occurs as a transient effect of rightfrontoparietal lesions, with bilateral ptosis (Averbuch-Heller et al 1996). Downgaze palsy.This occurs with bilateral dorsomedial lesions of the rostralintrastitial nucleus of the medial longitudinal fasciculus (Buttner-Ennever et al1982;Bogousslavsky et al 1988). It is hypothesized that bilateral lesionsextending laterally impair upgaze also; therefore, selective downgaze palsy mustrequire a small and specific lesion, accounting for its rarity (Pierrot-Deseilligny etal 1982). Convergence, accommodative responses, and the pupillary nearresponse may all be impaired too (Cogan 1974). The pupillary light response can

be affected (Cogan 1974)or preserved (Pierrot-Deseilligny et al 1982). Skewdeviation and internuclear ophthalmoplegiacan occur (Cogan 1974). Downgaze is also affected by akinetic movement disorders, most typicallyprogressive supranuclear palsy(Cogan 1974). Combined up and down gaze palsy. The lesions involve the riMLF or theinterstitial nucleus of Cajal, most frequently bilaterally. In the less commonunilateral cases the lesion of the ipsilateral riMLF likely also interruptsdecussating fibers from the contralateral riMLF. Vertical vestibulo-ocularresponse frequently appears normal (Buttner-Ennever et al 1982;Page et al

palsy: saccades and pur

- Progressive supranucleapalsy: vestibular verticaeye movements

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1982;Pierrot-Deseilligny et al 1982;Yamamoto 1989;Bogousslavsky et al1990), but is sometimes absent (Beversdorff et al 1995)or impaired in 1direction alone (Guberman and Stuss 1983). Torsional and vertical nystagmusmay occur if the interstitial nucleus of Cajal is involved (Ranalli and Sharpe1988). Bell phenomenon can be absent (Page et al 1982)or inverted (Ranalli andSharpe 1988). Pretectal syndrome.This syndrome combines vertical supranuclear palsy,affecting either upgaze alone or both upgaze and downgaze, sparing vestibulo-

ocular response range, with a variable number of other signs (Keane 1990).These include light-near pupillary dissociation, with loss of the pupillary lightreactions from damage to the pretectum, Collier lid retraction sign, and skewdeviation. Horizontal conjugate eye movements are spared but there may beesotropia, exotropia, or convergence insufficiency. An unusual convergence-retraction nystagmus is pathognomonic. Fragmentary pretectal syndrome, withonly some of the above features, is common. Vertical one-and-a-half and other syndromes.Rarely a patient may have avertical impairment that spares only a single direction in 1 eye. Supranuclearbilateral downgaze paresis affecting all movements combined with monocularelevator palsy occurs with bilateral midbrain infarction(Deleu et al 1989). Theopposite, supranuclear bilateral upgaze paresis with monocular depressor palsy,

has also been described with unilateral midbrain infarctions (Bogousslavsky andRegli 1984;Miyashita et al 1987;Gulyas et al 2006). A unique case of ipsilateralmonocular elevator paresis and contralateral monocular depressor paresis,combined with mild bilateral ptosis, has been reported (Wiest et al 1996).Finally, a patient with supranuclear vertical palsy combined with completeophthalmoplegia of 1 eye has been described, with the ophthalmoplegiaattributed to a combination of oculomotor nerve palsyand pseudoabducens palsy(Thurtell et al 2009). Vertical congenital ocular motor apraxiais rare (Ro et al 1989;Brown andWillshaw 2003)and has been related to perinatal hypoxia (Hughes et al 1985)orbilateral mesencephalic-diencephalic lesions (Ebner et al 1990). Combinedvertical and horizontal ocular motor apraxiacan be seen in conditions such as

Joubert syndrome(Tusa and Hove 1999).

Clinical vignette A 69-year-old orthopedic surgeon suffered a stroke 6 months prior toevaluation. He presented with somnolence, imbalance, and diplopia. His initialexamination notes documented a right third nerve palsy and ataxic gait. Hissymptoms had improved but still persisted. The drowsiness responded tomethylphenidate. He had no anisocoria in bright light or darkness, and light reactions were intact.He had no ptosis, but developed lid retraction in attempted upgaze (Collier sign).Neither eye elevated more than 10% past midline, whether saccades, pursuit,

Doll eye maneuver, or Bell phenomenon were tried. Downgaze was also absentwith the exception of Doll eye maneuver, indicating that downward vestibulo-ocular response was relatively spared. The right eye had only 50% of normaladduction range, which was not improved by convergence. Horizontal saccadesand pursuit were otherwise normal. He was intermittently drowsy duringexamination, and his gait showed a wide-based ataxia requiring support. His ocular signs represented a combination of right third nuclear palsy, withimpaired adduction and bilateral elevation paresis, and a supranuclear downgazepalsy. The sparing of downward vestibulo-ocular response confirmed that this
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was a supranuclear defect, most likely due to involvement of the riMLF.Conversely, the lack of upward vestibulo-ocular response suggested that upgazepalsy is not due only to riMLF or interstitial nucleus of Cajal involvement butlikely the third nucleus itself. Third nuclear lesions affected both the ipsilateralsuperior rectus subnucleus (which innervates the contralateral eye) anddecussating fibers from the contralateral superior rectus subnucleus. His MRI showed bilateral lesions of the thalamomesencephalic junction,consistent with a top of the basilar stroke affecting both paramedian thalamic

arteries.

Etiology Infarction in the territory of the paramedian artery (a top of the basilarsyndrome) can cause any vertical gaze palsy. This can occur with unilaterallesions (Alemdar et al 2006). Brainstem ischemia is the likely mechanism ofslowed saccadesor reduced gaze range in vertical or all directions followingcardiac surgery, though MRIand CT imaging are usually unremarkable (Solomonet al 2008). Diffusion-weighted imaging can be particularly helpful with thisdiscrete lesion (Seifert et al 2004). Thalamic hemorrhage, especially withintraventricular extension, is a common cause (Steinke et al 1992). Associated

signs of fixed pupils, horizontal gaze problems, and skew deviation are morecommon with hemorrhages than infarcts. Other causes include degenerative conditions, most commonly progressivesupranuclear palsy. In this condition, gaze palsy and early posturalinstability may be a marker of a variant with shorter lifespan and different tauisoforms (Williams et al 2005a). Demonstration of slowing of both vertical andhorizontal saccades on eye movement recordings may be useful in differentiatingthis condition from Parkinson disease(Pinkhardt et al 2008). Comparisons of thepathology of parkinsonian syndromesshow greater midbrain atrophy when thereare vertical gaze abnormalities to point to progressive supranuclear palsy(Songet al 2011). There is accumulating evidence that progressive supranuclear palsyis a disorder involving the tau protein primarily (Dickson et al 2007);

interestingly, vertical gaze palsy has also been reported in other tauopathies,such as corticobasal degeneration(Klodowska-Duda et al 2006); indeed, up tohalf of patients with corticobasal degeneration have vertical gaze palsies early intheir course (Ling et al 2010). Other more rare degenerative conditions withvertical gaze palsy include parkinsonism-dementia complex (Oyanagi et al 2000),sometimes of the frontotemporal variety (Slowinski et al 2007), dentatorubralpallidoluysian atrophy (Espay et al 2006), and rarely dementia with Lewy bodies(Nakashima et al 2003;Clerici et al 2005). Mild vertical gaze palsy is seen inabout a quarter of patients with multiple system atrophy(Anderson et al 2008).A variant of amyotrophic lateral sclerosiscauses slowed vertical saccades(Averbuch-Heller et al 1998;Knirsch et al 2000)and vertical gaze palsy (Ushioet al 2009).

Infectious or para-infectious conditions include paraneoplasticencephalitis(Bennett et al 1999), prion disease(Oba et al 2000;Kovacs et al 2011), Whippledisease(Pruss et al 2007), and HIV encephalitis(Kitthaweesin 2002). Verticalgaze palsy can also occur uncommonly in sporadic or familial variants ofCreutzfeldt-Jakob disease(Prasad et al 2007). Genetic defects with vertical gaze palsy include a number of conditions thatshare a predominance of cerebellar features. Chief among these is Niemann-Picktype C (Cogan et al 1981). This presents in childhood (average age atdiagnosis is 10 years) and is preceded by jaundice and hepatosplenomegaly at
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birth in about half of patients; vertical gaze palsy is present in 70% to 80% ofpatients (Garver et al 2007;Patterson et al 2013). Juvenile and adult-onsetcases are increasingly recognized: visceral signs are less common, and casespresent with initial psychiatric or cognitive problems, dyslexia, cerebellar ataxiaand dysarthria, dysphagia, and, less commonly, seizures and dystonia(Vanier2010). In a cohort of patients with young adultonset degenerative ataxia,cognitive decline, and vertical gaze palsy, 4 of 13 (31%) had Niemann-Pick typeC (Schicks et al 2013). Dementia and death in mid-adulthood are common, but

the natural history is highly variable across subjects. In 90% of patients, this isdue to a mutation in the NPC1 gene, the remainder are due to NPC2 mutations.The NPC proteins are involved in intracellular trafficking of cholesterolsystemically and sphingolipidsin the brain (Vanier 2010). Another rareautosomal recessive condition consists of cerebellar ataxia and dysarthria,myoclonusand seizures, and sensory neuropathy and upgaze palsy (Straussberget al 2005). A hereditary degenerative disorder has been described inNewfoundland, with manifestations in childhood or early adulthood of impaireddowngaze followed by lower limb spasticityand then ataxia, dysarthria, anddysphagia(Grewal et al 2004). Other genetic conditions fall under the rubric of early-onset parkinsonism. KuforRakeb disease is an autosomal recessive condition with levodopa-responsive

parkinsonism, pyramidal signs, dementia, and upgaze palsy, with onset in theteens and often death in early adulthood; it has been reported in Jordan(Williams et al 2005b)and Chile and has been associated with mutations of theATP13A2 gene at the PARK9 locus (Behrens et al 2010). The vertical gaze palsyis useful in distinguishing this entity from a number of other early-onsetautosomal recessive parkinsonian syndromes (Paisan-Ruiz et al 2010). Perrysyndrome is a rare autosomal dominant Parkinsonism with respiratory failure dueto a mutation in the DCTN1 gene, and in some can be associated with adowngaze palsy (Newsway et al 2010). Pantothenate kinase-associatedneurodegeneration, a slowly progressive disease beginning in childhood andcharacterized by dystonia, parkinsonism, spasticity, retardation, and visual loss,can also cause impaired vertical saccades and pursuit (Bozi et al 2009).

Rare causes include encephalitis, brain abscess, trauma, transtentorialherniation, and Wernicke encephalopathy (Keane 1990). There is one case ofpachymeningitis associated with rheumatoid arthritis mimicking progressivesupranuclear palsy (Aguilar-Amat et al 2011). Iatrogenicvertical gaze palsy hasbeen described after implantation of depth electrodes for stimulation,presumably due to damage to the riMLF(Ackermans et al 2007).

Pathogenesis and pathophysiology The rostral mesencephalon has medial structures that provide vertical gazeinputs to the ocular motor nuclei (Pierrot-Deseilligny et al 1982;Ranalli andSharpe 1988;Bhidayasiri et al 2000).

The riMLF has excitatory burst neurons for vertical saccades. It receives controlinputs from long-lead burst and omnipause neurons in the paramedian pontinereticular formation. The neurons for upward saccades are lateral to those fordowngaze (Buttner-Ennever et al 1982;Pierrot-Deseilligny et al 1982;Ranalliand Sharpe 1988). This may explain why upgaze is sometimes spared withbilateral riMLFlesions. An alternative explanation is that upgaze motor neuronsreceive bilateral input from these prenuclear structures, whereas downgaze onesdo not and, hence, are more vulnerable to partial destruction of the riMLFs(Bhidayasiri et al 2000).
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The interstitial nucleus of Cajal performs several functions. It mediates verticalsmooth pursuit with inputs from lower brainstem and cerebellar structures thattraverse the brachium conjunctivum and the medial longitudinal fasciculus. Italso takes vertical and torsional velocity commands to determine the firing ratesto hold gaze steady in eccentric vertical positions. Although the interstitial nucleus of Cajal forms part of an indirect verticalvestibulo-ocular response pathway, the pathway projects from the vestibularnuclei directly to the third and fourth nuclei through the medial longitudinal

fasciculus and the brachium conjunctivum. The projections to ocular motor nuclei from the riMLF and interstitial nucleus ofCajal for upward movements decussate in the posterior commissure, but notthose for downgaze.

Epidemiology Not applicable.

Prevention Not applicable.

Differential diagnosis Graves ophthalmopathy often causes restriction of the inferior recti,occasionally mimicking an upgaze palsy. Furthermore the lid retraction in Gravescan be confused with Collier sign. A key difference is that the lid retraction inGraves often increases in downgaze (lid lag) rather than in upgaze. Proptosis andconjunctival injection are other helpful clues pointing to thyroid disease (Bartleyand Gorman 1995). Most patients are hyperthyroid, but some are hypothyroid,and 15% are even euthyroid (Yeatts 1995). Seventy-five percent already have ahistory of thyroid dysfunction (Gorman 1983), but this can followophthalmopathy months later.

Myasthenia gravis can also mimic gaze palsy, though this is usually anasymmetric disease with complaints of diplopia. Variability and fatigability arekey aspects that point to a neuromuscular junction problem. Ptosis developseventually in most patients with myasthenia. Proximal limb or bulbar weaknesswith fatigability are helpful, but will not be present in ocular myasthenia. Theedrophonium test, single-fiber electromyography, repetitive nerve conductionstudies, and assays for antibodies to acetylcholine receptor are useful tests, butthe sensitivity of each of these is only 70% or less when myasthenia is confinedto the eye muscles (Vincent and Newsom-Davies 1980;Evoli et al 1988;Morel etal 1988). Botulism is another neuromuscular junction problem that affects the ocularmotor system. Signs of cholinergic autonomic hypofunction such as dilated

unreactive pupils, urinary retention, and decreased bowel sounds are importantclues. Miller-Fisher syndrome is a triad of ophthalmoplegia, ataxia, and areflexia,sometimes following an upper respiratory or gastrointestinal tract infection by afew weeks (Berlit and Rakicky 1992). A symmetric paresis of upgaze is acommon early presentation, though with time other eye movements are usuallyaffected too (Al-Din et al 1994). Sometimes the ocular motor defects occurwithout ataxia, and rare cases of vertical gaze palsy in this situation have beendescribed (Lee et al 2008). Anti-GQ1b antibodiesare present in serum (Chiba et
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al 1992;1993;Willison et al 1993).

Diagnostic workup Imaging of the midbrain and the thalamomesencephalic junction is key to thediagnosis of vertical gaze palsies. MRIis preferred, and will detect most caseswith vascular or neoplastic origin. Gaze palsy in parkinsonian conditions likeprogressive supranuclear palsycorrelate with midbrain atrophy, creating the

morning glory sign (Adachi et al 2004). In cases with gradual or subacute onset, disorders of muscle, neuromuscularjunction, or peripheral nerves should be considered. Their tests are listed in thesection on differential diagnosis. Niemann-Pick type C might be suspected fromcognitive and cerebellar dysfunction associated with elevation in serumtransaminases and hepatosplenomegaly (Tyvaert et al 2005), in which case abone marrow biopsy and skin fibroblast assay for sphingomyelinase activity areindicated. . Genetic testingcan also be done for this condition. Widespreadsigns of motor neuron dysfunction are usually present in the patients withamyotrophic lateral sclerosisand can be confirmed with electromyography.

Prognosis and complications Prognosis varies with cause. With thalamic hemorrhages, there is usually someresolution over several weeks. Shunting in hydrocephalushas variable effect(Keane 1990;Niwa et al 2006).

Management After treatable causes have been investigated and managed, symptomatictreatment can be considered. Some patients with limited downgaze complain oftrouble reading. This can be helped with base-down prisms in both lenses of theirreading glasses. Upgaze limitation rarely requires symptomatic treatment.Unilateral prisms can help eliminate diplopiain those with asymmetric ocular

alignment if there is an associated skew deviation or third nerve palsy. Somephysiotherapists have suggested that eye movement exercises can improve gazecontrol in progressive supranuclear palsy(Zampieri and di Fabio 2009), althoughthis is not widely accepted. Miglustat is being widely evaluated as a treatment forNiemann-Pick disease type C(Patterson et al 2007). Eye movement recordingshave been used as a component of the monitoring of efficacy of treatment(Patterson et al 2007;Scheel et al 2010).

Pregnancy Not applicable.

Anesthesia Not applicable.

ICD codesICD-9:Palsy of conjugate gaze: 378.81Deficiencies of saccadic eye movements: 379.57
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Deficiencies of smooth pursuit movements: 379.58ICD-10:Palsy of conjugate gaze: H51.0Nystagmus and other irregular eye movements: H55

Associated disordersAtaxia-telangiectasia

Progressive supranuclear palsy

Related summariesNiemann-Pick disease type C

Differential diagnosisGraves ophthalmopathythyroid dysfunctionmyasthenia gravisneuromuscular junction problembotulism

Miller-Fisher syndrome

DemographicsFor more specific demographic information, see the Epidemiology, Etiology, andPathogenesis and pathophysiology sections of this clinical summary.

Age

0-01 month01-23 months02-05 years06-12 years13-18 years

19-44 years45-64 years65+ years

Population

None selectively affected.

Occupation

None selectively affected.

Sex

male=female

Family history

family history may be obtained

Heredity

heredity may be a factor

References citedAckermans L, Temel Y, Bauer NJ, Visser-Vandewalle V; Dutch-Flemish Tourette
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mimicking progressive supranuclear palsy. Neurologist 2011;17(3):136-40.Al-Din N, Anderson M, Eeg-Olofsson O, Trontelj T. Neuro-ophthalmicmanifestations of the syndrome of ophthalmoplegia, ataxia, and areflexia: areview. Acta Neurol Scand 1994;89:157-63.Alemdar M, Kamaci S, Budak F. Unilateral midbrain infarction causing upwardand downward gaze palsy. J Neuroophthalmol 2006;26(3):173-6.Anderson T, Luxon L, Quinn N, Daniel S, Marsden CD, Bronstein A. Oculomotorfunction in multiple system atrophy: clinical and laboratory features in 30patients. Mov Disord 2008;23(7):977-84.

Averbuch-Heller L, Helmchen C, Horn A, Leigh R, Buttner-Ennever J. Slowvertical saccades in motor neuron disease: correlation of structure and function.Ann Neurol 1998;44:641-8.Averbuch-Heller L, Stahl J, Remler B, Leigh R. Bilateral ptosis and upgaze palsywith right hemispheric lesions. Ann Neurol 1996;40:465-8.Bartley G, Gorman C. Diagnostic criteria for Graves' ophthalmopathy. Am JOphthalmol 1995;119:792-5.Behrens MI, Brggemann N, Chana P, et al. Clinical spectrum of Kufor-Rakeb

syndrome in the Chilean kindred with ATP13A2 mutations. Mov Disord2010;25(12):1929-37.Bennett J, Galetta S, Frohman L, et al. Neuro-ophthalmologic manifestations of aparaneoplastic syndrome and testicular carcinoma. Neurology 1999;52:864-7.Berlit P, Rakicky J. The Miller Fisher syndrome. Review of the literature. J ClinNeuroophthalmol 1992;12:57-63.Beversdorff D, Jenkyn L, Petrowski J, Cromwell L, Nordgren R. Vertical gazedparalysis and intermittent unresponsiveness in a patient with athalamomesencephalic stroke. J Neuro-ophthalmol 1995;15:230-5.

Bhidayasiri R, Plant G, Leigh R. A hypothetical scheme for the brainstem controlof vertical gaze. Neurology 2000;54:1985-93.Bogousslavsky J, Miklossy J, Deruaz J, Regli F, Assal G. Unilateral leftparamedian infarction of thalamus and midbrain: a clinico-pathological study. JNeurol Neurosurg Psychiatry 1986;49:686-94.Bogousslavsky J, Miklossy J, Regli F, Janzer R: Vertical gaze palsy and selective
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unilateral infarction of the rostral interstitial nucleus of the medial longitudinalfasciculus (riMLF). J Neurol Neurosurg Psychiatry 1990;53(1):67-71.Bogousslavsky J, Regli F. Upgaze palsy and monocular paresis of downward gazefrom ipsilateral thalamo-mesencephalic infarction: a vertical "one-and-a-half"syndrome. J Neurol 1984;231(1):43-5.Bogousslavsky J, Regli F, Uske A. Thalamic infarcts: clinical syndromes, etiology,

and prognosis. Neurology 1988;38(6):837-48.Bozi M, Matarin M, Theocharis I, Potagas C, Stefanis L. A patient withpantothenate kinase-associated neurodegeneration and supranuclear gaze palsy.Clin Neurol Neurosurg 2009;111(8):688-90.Brown H, Willshaw HE. A case of disturbed vertical gaze. Eur J Paediatr Neurol2003;7(4):173-5.Buttner-Ennever J, Buttner U, Cohen B, Baumgartner G. Vertical gaze paralysisand the rostral interstitial nucleus of the medial longitudinal fasciculus. Brain1982;105:125-49.

Castaigne P, Lhermitte F, Buge A, Escourolle R, Hauw J, Lyon-Caen O.Paramedian thalamic and midbrain infarcts: clinical and neuropathological study.Ann Neurol 1981;10:127-48.Chiba A, Kusunoki S, Obata H, Machinami R, Kanazawa I. Serum anti-GQ1b IgGantibody is associated with ophthalmoplegia in Miller Fisher syndrome andGuillain-Barr syndrome. Neurology 1993;43:1911-7.Chiba A, Kusunoki S, Shimizu T, Kanazawa I. Serum IgG antibody to gangliosideGQ1b is a possible marker of Miller Fisher syndrome. Ann Neurol 1992;31:677-9.

Clerici F, Ratti PL, Pomati S, et al. Dementia with Lewy bodies with supranucleargaze palsy: a matter of diagnosis. Neurol Sci 2005;26:358-61.Cogan D. Paralysis of downgaze. Arch Ophthalmol 1974;91:192-9.Cogan D, Chu F, Bachman D, Barranger J. The DAF syndrome. Neuro-ophthalmology 1981;2:7-16.Deleu D, Buisseret T, Ebinger G. Vertical one-and-a-half syndrome. Arch Neurol1989;46:1361-3.Dickson DW, Rademakers R, Hutton ML. Progressive supranuclear palsy:

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