We describe a patient with downbeat nystagmus (DBN) evoked only by eye closure. Brain and spinal cord magnetic resonance imaging revealed a T2 paramedian lesion in the left lower basis pontis and other white matter lesions consistent with multiple sclerosis. One potential mechanism for DBN in this case involves transverse ephaptic spread of excitation from areas that subserve coordinated lid closure to the decussating ventral tegmental tract.info:eu-repo/semantics/publishedVersio

Amorim, M

Cunha, L

Lemos, J

Paiva, A

Pereira, D

Santiago, B

João Lemos

Daniela Pereira

Margarida Amorim

Beatriz Santiago

António Paiva

Luís Cunha

Crossref

Journal of Neuro-Ophthalmology

Downbeat Nystagmus Elicited by Eyelid Closure

Name not available

Downbeat Nystagmus Elicited by Eyelid ClosureJoão Lemos, MD, Daniela Pereira, MD, Margarida Amorim, MD, Beatriz Santiago, MD,António Paiva, PhD, Luís Cunha, PhDAbstract: We describe a patient with downbeat nystagmus(DBN) evoked only by eye closure. Brain and spinal cordmagnetic resonance imaging revealed a T2 paramedianlesion in the left lower basis pontis and other white matterlesions consistent with multiple sclerosis. One potentialmechanism for DBN in this case involves transverseephaptic spread of excitation from areas that subservecoordinated lid closure to the decussating ventral tegmentaltract.Journal of Neuro-Ophthalmology 2014;34:350–353doi: 10.1097/WNO.0000000000000123© 2014 by North American Neuro-Ophthalmology SocietyD ownbeat nystagmus (DBN) is an ocular motor disor-der with a slow spontaneous upward drift and a com-pensatory fast phase directed downward. If occurringspontaneously, it is most commonly caused by lesions ofthe cerebellar ﬂocculus or paraﬂocculus, which are believedto disinhibit the upward vestibular system. Less commonly,DBN is associated with brainstem lesions located in medullaoblongata and/or pontine tegmentum, strategically involv-ing the paramedian tract neurons, medial vestibular neurons,and/or its efferent tracts (1–8). Evoked forms of DBN exist,such as following head shaking in patients with focal pon-tine tegmentum infarction (9) and dorsomedial medullaoblongata demyelination (10). DBN occurring with eyeclosure has been reported in 2 patients in the pre–magneticresonance imaging (MRI) era. Both had presumed periph-eral vestibulopathy (11). DBN with eye closure may alsooccur in a small percentage of normal individuals (12). Wedescribe a patient with dizziness and DBN occuring onlywith eyelid closure in whom a localized paramedian lesionof the lower basis pontis was detected.CASE REPORTA 43-year-old woman with no neurological history devel-oped subacute asymmetric weakness and paresthesias of thelower limbs and urinary retention. Two weeks later, sheexperienced the sensation of rhythmic vertical eye move-ments and sustained to- and-fro- imbalance provoked onlyby voluntary eye closure. Examination demonstrated a T10sensory level with impaired lower limb proprioception andvibration. She had bilateral extensor plantar responses.Muscle stretch reﬂexes were reduced bilaterally. Limbcoordination was intact. To- and fro- truncal unsteadinesswas evident when seated with a tendency to fall backwardsonly with eyes closed.Visual acuity was 20/20 in both eyes, pupils had normalreactions, and the fundi were normal. The patient had normaleye alignment and full ocular motility without spontaneous,gaze-evoked, positional, hyperventilation-induced, or head-shaking nystagmus with or without ﬁxation (Frenzel lens).Video-guided direct occlusive ophthalmoscopy (13) did notshow any nystagmoid movements (See SupplementalDigital Content, Video, http://links.lww.com/WNO/A98).Pursuit was smooth, saccades showed normal range andvelocity, and the horizontal and vertical head thrust testwas normal. Continuous ryhthmic vertical ocular excursionswere evident under closed lids, associated with fore and aftpostural instability (See Supplemental Digital Content,Video, http://links.lww.com/WNO/A98). There was noassociated eyelid muscular contraction. No abnormal move-ments of the soft palate were seen either with eyes open orclosed.Two weeks after onset of symptoms, brain MRI revealeda small left paramedian lesion located at the level of theDepartments of Neurology (JL, BS, LC), Neuroradiology (DP), andOtorhinolaryngology (MA, AP), Coimbra University Hospital Center,Coimbra, Portugal.The authors report no conﬂicts of interest.Presented as a poster at the 39th Annual NANOS Meeting, February11–16, 2013, Snowbird, UT.Supplemental digital content is available for this article. Direct URLcitations appear in the printed text and are provided in the full textand PDF versions of this article on the journal’s Web site (www.jneuro-ophthalmology.com).Address correspondence to João Lemos, MD, Department of Neu-rology, Coimbra University Hospital Center, Praceta Professor MotaPinto, Coimbra 3000-075, Portugal; E-mail: merrin72@hotmail.com350 Lemos et al: J Neuro-Ophthalmol 2014; 34: 350-353Original ContributionCopyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. lower basis pontis near the pontomedullary junction,without involvement of the tegmentum. This lesion showeda hyperintense signal on T2 imaging and nodular enhance-ment (Fig. 1). No other lesions were detected in the cere-bellum, medulla, or midbrain. However, 9 hyperintenselesions were present in the hemispheric periventricularwhite matter with an enhancing thoracic cord hyperinten-sity. Cerebrospinal ﬂuid studies demonstrated a normal cellcount, glucose, and protein levels with no oligoclonal bands.The multiplicity, distribution and the presence of bothenhancing and nonenhancing lesions were highly suggestiveof multiple sclerosis.On 2 separate occasions, eye movements were recordedin light, darkness, and in the absence of ﬁxation by video-nystagmography (VNG) (VNG Ulmer version C4, resolu-tion of 0.1°, sampling rate of 100 Hz; Synapsys, Marseille,France) and in light, darkness, and with eyes closed usingsimultaneous horizontal and vertical electronystagmography(ENG) (4-channel Hortman CNG analyzer, DC-coupled,sampling rate of 50 Hz; Hortmann Neuro-otometrie,Neckartenzlingen, Germany). Using VNG, there was noevidence of spontaneous nystagmus in primary position inlight (Fig. 2A), dark, or absence of ﬁxation. Horizontal 20°and vertical 15° saccades at a frequency of 0.3 Hz hadnormal latency, velocity, and accuracy. Sinusoidal horizon-tal 30° pursuit at a frequency of 0.3 Hz showed normalgain. Vertical pursuit, caloric and rotational testing were notperformed. ENG with eyes open in light and in darkness(Fig. 2B) failed to demonstrate spontaneous nystagmus inprimary position, but with eyes closed, there was persistentand reproducible DBN (slow phase velocity 18°/s; ampli-tude 3.8°; frequency 1.9°/s) (Fig. 2C).The patient was hospitalized and treated with intrave-nous methylprednisolone 1,000 mg daily for 5 days and wassubsequently started on interferon beta-1b for probablemultiple sclerosis. She refused any symptomatic treatmentfor nystagmus. After 9 months, motor and sensoryinvolvement had completely resolved, whereas DBN andunsteadiness evoked by eye closure were unchanged. Thepatient continued to show no evidence of palatalmyoclonus.DISCUSSIONDBN caused by focal brainstem lesions (3,4,6–10) has beenreported in a variety of clinical settings: spontaneous DBN(3,5–8), DBN (perverted) after horizontal head shakingwith (10) or without associated spontaneous nystagmus(9), convergence-induced DBN in a patient with spontane-ous upbeat nystagmus (UBN) (4), and spontaneous DBNreplacing UBN (2). The presumed brainstem lesions caus-ing DBN were located in the medulla (3–5), speciﬁcally inthe paramedian medullary region (2,6,10), pontomedullaryjunction (7), and the pontine paramedian tegmentum (8,9).The proposed mechanism for DBN requires a hyperac-tive vestibular system carrying anterior canal information,including the superior vestibular nucleus and its afferentconnections to the third nerve subnucleus through themedial longitudinal fasciculus, brachium conjuntivum, andthe ventral tegmental tract (VTT) (14). Generation ofupward slow phases is followed by corrective downwardquick phases creating DBN (1).This series of events may occur through 2 potentialpathways. First, paramedian tract neurons, excite theﬂoccular/paraﬂoccular region that inhibits vestibular path-ways carrying anterior canal information (6,8). With a lesionof the paramedian tract neurons, this inhibition is lost pro-moting hyperactivity of the anterior canal system. Alter-nately, damage of the downward vestibular systemcarrying posterior canal information constituted by themedial vestibular neurons and their afferent connectionswould lead to hyperactivity of the anterior canal systemand DBN (3,14).Our patient had an isolated paramedian lesion in basispontis without apparent involvement of neighboring struc-tures. However, VTT is located near the transition betweenFIG. 1. T2 axial (A) and postcontrast T1 sagittal (B) mag-netic resonance imaging shows a hyperintense lesion(arrow) in the vicinity of the crossing tegmental tract.Lemos et al: J Neuro-Ophthalmol 2014; 34: 350-353 351Original ContributionCopyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. basis and tegmentum in the pons, particularly at the level ofits decussation (15), which coincides with our patient’slesion. Although VTT damage and subsequent hypoactivityis the pathophysiological mechanism for UBN in a numberof case reports (9,14–16), its hyperactivity theoreticallycould generate DBN. We believe that DBN with eyelidclosure is due to transverse emphatic spread of excitationfrom a demyelinating plaque in paramedian pons, to bothVTTs (or to its decussation). By activating this tract, a rel-ative hyperactivity in the ﬁnal vestibular pathways convey-ing anterior canal signals is promoted, inducing upwardslow eye movement and compensatory fast-phase down-ward beating movement, resulting in DBN. Additionally,normal upward deviation of the eye under eye closure (Bellphenomenon) could promote an addictive effect (17).Paroxysmal attacks are a well-known feature in patientswith multiple sclerosis, and transversely spreading ephapticactivation of axons in partially demyelinated lesions is oneof the mechanisms that may explain these phenomena (18).These attacks may be precipitated by movement of thelimbs (19) or neck, hyperventilation, rising quickly (19),visual perception of movement (20), lateral gaze (21), ortouch. In our patient, voluntary eye closure provoked sus-tained and reproducible DBN. In animal experimental data,eyelid closure was achieved not only with electrical stimu-lation of pontine tegmentum, but also with stimulationsmade more ventrally and mesially (22). The lesion in ourpatient could potentially involve the areas that subservecoordinated lid closure in the midpons. Their activationcould excite contiguous tracts including the VTT, by trans-verse ephaptic spread of excitation. With eye opening, thisspread of excitation would cease, and DBN abates (Fig. 3).FIG. 2. Vertical and horizontal eye position (degrees) overtime (seconds) from monocular recordings of the left eye. A.Videonystagmography with both eyes open in light, ﬁxatinga target at 60 cm. No nystagmus is seen. B. Electro-nystagmography (alternate current) with both eyes open inthe dark in the absence of ﬁxation. No nystagmus is seen.C. Electronystagmography (alternate current) with both eyesclosed. DBN is seen with exponentially increasing slowphase velocity waveform in the majority of the complexes.No consistent horizontal component is seen. Eye move-ments up and left are represented by an upward deﬂectionof the tracing, whereas down and right are represented bya downward deﬂection. The upper traces in (A), (B), and (C)represent the vertical component (v), whereas the lowertraces represent the horizontal component (h).FIG. 3. Schematic drawing of brainstem, showing the left paramedian pontine lesion, regions that subserve eye closure(dotted areas) and the 2 ventral tegmental tracts connecting the superior vestibular nucleus with the third nerve nucleus,possibly decussating at the level of midpons. When both eyes are open (A), no pathological vestibular imbalance occurs.Immediately after eye closure (B), ephaptic spread of excitation will activate the contiguous ventral tegmental tracts, causingparoxysmal vestibular imbalance and downbeat nystagmus. 3 = third nerve nucleus; sr = superior rectus motoneurons; io =inferior oblique motoneurons; VTT = ventral tegmental tract; 8 = vestibular nucleus; svn = superior vestibular nucleus. Theupper, mid, and lower rectangles in (A) and (B) depict the midbrain, pons, and medulla, respectively.352 Lemos et al: J Neuro-Ophthalmol 2014; 34: 350-353Original ContributionCopyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. An alternative mechanism is that our patient developeda form of oculopalatal tremor (OPT). Eye closure has beenreported to provoke pendular nystagmus in a series ofpatients with OPT, showing no nystagmus with eyes open(23). However, the presence of nystagmus with an apparentjerk component in the majority of the ENG complexes andthe absence of damage of Mollaret triangle structures and/orinferior olivary hypertrophy on MRI makes this diagnosisless likely in our patient. After 9 months of follow-up, thereis still no evidence of palatal myoclonus, either with eyesopen or closed (24). A ﬁnal possibility accounting for thepresence of DBN in our patient could be based on involve-ment of the paramedian tract neurons and/or its connec-tions instead of the proposed hyperexcitation of both VTTs.Involvement of paramedian tract neurons in our case couldhave to have escaped detection on MRI (25).ACKNOWLEDGMENTSThe authors gratefully acknowledge Dr Eric Eggenbergerfor his helpful comments and suggestions.REFERENCES1. Leigh RJ, Zee DS. Diagnosis of nystagmus and saccadicintrusion. In: Leigh RJ, Zee DS, eds. Neurology of EyeMovements. 4th edition. New York, NY: Oxford UniversityPress, 2006:475–558.2. 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Downbeat nystagmus elicited by eyelid closure

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Downbeat nystagmus elicited by eyelid closure

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