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Clinical commentaryEpileptic Disord 2018; 20 (4): 283-8

Epileptic ictal strabismus:a case report and reviewof the literatureFrancesco Brigo 1,2, Franco Alessandrini 3,Giammario Ragnedda 2, Piera Canu 2, Veronica Tavernelli 2,Arianna Bratti 2, Raffaele Nardone 2,4

1 Department of Neurosciences, Biomedicine, and Movement Sciences,University of Verona2 Division of Neurology, Franz Tappeiner Hospital, Merano3 University Hospital Verona, Department of Neuroradiology, Verona, Italy4 Department of Neurology, Christian Doppler Medical Centre, Paracelsus MedicalUniversity, Salzburg, Austria

Received January 30, 2018; Accepted May 01, 2018

ABSTRACT – Ictal strabismus, sometimes associated with epileptic nystag-mus, is an extremely rare epileptic phenomenon, suggestive of corticalinvolvement in monocular eye movement control. We describe a patientwith ictal disconjugate contraversive horizontal eye deviation of cortical ori-gin as the main clinical feature of a focal seizure. A 17-year-old, previouslyhealthy woman had a seizure characterized by initial rightward conju-gate eye deviation, followed by convergent strabismus due to adductionof the right eye towards the nose without conjugate left eye abduc-tion (esotropia), forced leftward head deviation with impaired awareness,and subsequent evolution into a bilateral tonic-clonic seizure. Postictaland interictal neurological status were unremarkable; more specifically,neuro-ophthalmological examination revealed no nystagmus or altered eyemotility. Ictal EEG showed a rhythmic theta activity over the right pos-terior temporal region, involving fronto-central regions when strabismusappeared. MRI showed cortical dysplasia in the right temporal lobe. Dueto the low spatial resolution of scalp EEG, we could not identify with preci-sion the symptomatogenic zone underlying ictal strabismus. However, theconcomitant appearance of rhythmic theta activity over the right fronto-

ersion with MRI perfusion sequences,in the right frontal eye field area, sug-obe. [Published with video sequence

ment, seizure, MRI, EEG, frontal lobe

IDEO ONLINE

central region and the leftward head vshowing cerebral blood flow increasegest involvement of the right frontal lon www.epilepticdisorders.com].

Key words: ictal strabismus, eye move

pileptic Disord, Vol. 20, No. 4, August 2018 283

orrespondence:rancesco Brigoepartment of Neurosciences,iomedicine, and Movement Sciences,niversity of Verona,iazzale L.A. Scuro,0 - 37134 Verona, Italydr.francescobrigo@gmail.com>

Ictal strabismus, sometimes associ-ated with epileptic nystagmus, isan extremely rare epileptic phe-nomenon, suggestive of corticalinvolvement in monocular eyemovement control (Galimberti etal., 1998; Thurtell et al., 2009; Schulz

et al., 2013). We describe a patientwith ictal disconjugate contraver-sive horizontal eye deviation ofcortical origin as the main clinicalfeature of a focal seizure. We alsoreview the extant literature on thisintriguing ictal phenomenon.

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17-year-old, previously healthy, right-handed womanas referred to our centre for diagnostic evalua-

ion. Four days earlier, at around 7.00 a.m., the sister,ho was sleeping in a nearby room, had heard theatient crying and when entering the patient’s roomhe had found her unable to react, with foaming of

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he mouth. The patient was brought to the emer-ency department, where brain MRI and routine bloodxaminations were performed yielding normal results.uring video-EEG recording, performed during the

ollowing days, the patient had a seizure characterizedy initial rightward conjugate deviation of the eyes,

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igure 1. At seizure onset (left arrow), the patient has a rightward hoctivity over the right posterior temporal region and rhythmic epileptioncomitant with the appearance of convergent strabismus due to aright arrow). The patient’s blinking (see blink artefact over frontal reaction to the sudden onset of diplopia due to ictal strabismus (whef double vision occurring immediately before loss of consciousnessensitivity: 7 �V; LF: 0.53 Hz; HF: 70 Hz; speed: 30 sec/page.

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ollowed by convergent strabismus due to adductionf the right eye towards the nose without conju-ate left eye abduction (esotropia) (figure 1, videoequence). When the strabismus appeared, the patientlinked. Tachycardia was also detected immediatelyfter the blink. Strabismus was not accompanied byystagmus. Afterwards, she did not react to external

Epileptic Disord, Vol. 20, No. 4, August 2018

rizontal conjugate eye deviation; the EEG shows rhythmic thetac activity from the right temporal to right fronto-central regions,dduction of the right eye without conjugate left eye abductionegions indicated by the right arrow) could be a semiconsciousn questioned postictally, the patient did not recall any symptom). Ictal tachycardia starts just after the blink.

ead, and then a bilateral tonic-clonic seizure. Postictalnd interictal status were unremarkable; more specif-cally, neuro-ophthalmological examination revealedeither nystagmus nor altered eye motility. After theeizure, she did not report having experienced anyouble vision or visual disturbance. Ictal EEG showed a

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Epileptic ictal strabismus

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Figure 2. (A) Coronal T1-weighted peri-ictal MRI multiplanar (MPR) reconstruction, (B) coronal thin-slice inversion recovery (IR), and(C) coronal thin-slice FSE T2 image of the patient whose previous MRI had been considered normal. Note the focal area of slightlythickened cortex and blurred cortical-subcortical junction in the posterior section of the right temporal lobe; 1-mm thin sections aresuggestive of cortical dysplasia.

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igure 3. (A) Peri-ictal axial T1-weighted MRI multiplanar (MPRmaging clearly shows focal cortical-subcortical cerebral bloodctal epileptic activity.

hythmic theta activity over the right posterior tem-oral region (related to rightward conjugate deviationf the eyes), spreading to ipsilateral fronto-centralegions when strabismus appeared. Treatment withevetiracetam up to 1,000 mg/day was started. Two

onths after the seizure described above, the patientxperienced a further epileptic seizure which was

pileptic Disord, Vol. 20, No. 4, August 2018

nwitnessed. The dosage of levetiracetam was there-ore increased to 1,500 mg/day without further seizuresoverall length of follow-up was 10 months). 3.0 Tesla

RI was performed peri-ictally, and images werecquired with a 3.0 Tesla MRI scanner (Signa Archi-ect, GE Healthcare, Milwaukee, WI). The protocolncluded a 3D MPR T1-weighted sequence (BRAVO),

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nstruction, and (B) axial DSC PWI image. Perfusion-weightedincrease in the right frontal eye field area, correlating with the

3D FLAIR (CUBE) sequence, a thin-slice (3.5-mm)xial DWI sequence, a thin-slice axial (3-mm) FSE T2-eighted sequence, coronal T2 and inversion recovery

IR) thin-section (1-mm) images, as well as a dynamicusceptibility contrast (DSC) MR perfusion sequencend a 3D MPR T1-weighted sequence after contrastedia administration. 3.0 Tesla MRI showed a focal

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rea of slightly thickened cortex and blurred cortical-ubcortical junction in the posterior section of theight temporal lobe, suggestive of cortical dysplasiafigure 2). Perfusion-weighted imaging showed focalortical-subcortical cerebral blood flow increase in theight frontal eye field area, correlating with the ictalpileptic activity (figure 3).

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e describe a patient with ictal strabismus due todduction of the right eye without conjugate left eyebduction (esotropia) as the main clinical feature offocal seizure. Ictal strabismus is an epileptic phe-

omenon which has been very rarely reported in theedical literature.

ntermittent esotropia associated with attacks of dizzi-ess has been interpreted as an equivalent of absences

n a three-year girl, with an EEG showing gener-lized symmetric and synchronous 3/s spike-waveischarges; squinting resolved completely after ther-py with ethosuximide (Gusek-Schneider et al., 2000).ther reports have described strabismus as a clinical

xpression of focal seizures.ischler and colleagues described a nine-year-old girlith strabismus due to in-turning of the right eye and

erk nystagmus on lateral gaze with preserved con-ciousness, associated with spike discharges in the leftarietal-occipital region (Tischler et al., 1996). Authorsttributed this clinical phenomenon to epileptic acti-ation of a smooth pursuit pathway.alimberti and co-workers described a patient withpileptic skew deviation, diplopia, and oscillopsiassociated with a right-beating nystagmus (Galimbertit al., 1998). The EEG recording showed epilep-ic activity over left parieto-occipital regions. Theuthors suggested that these ocular motor signs werederived from an ictal activation of the vestibular cor-ex, which in turn activated descending projectionso the vestibular nuclei, leading to both a dynamicright-beating nystagmus) and a static (skew deviation)estibular imbalance” (Galimberti et al., 1998).hurtell and colleagues described two epilepsyatients with ictal strabismus occurring during elec-

rical stimulation of the frontal eye fields or duringocal seizures spreading from the supero-posteriorylvian bank to the ipsilateral frontal lobe (Thurtellt al., 2009). As in the patient we describe, the inter-

ctal neuro-ophthalmological findings were normal,nd neuroimaging did not show any abnormality inhe brainstem. Hence, the authors concluded that theortical frontal eye field plays a role in both con-ralateral version and vergence eye movements. In thisegards, Rasmussen and Penfield had already observedhat stimulation of the precentral gyrus immediatelynterior to the central sulcus (Area 8) resulted in con-ralateral eye deviation (Rasmussen and Penfield, 1948),

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lthough less often it could also result in convergenceSmith, 1944). Subsequently, Jampel (1960) reportedhat stimulation of the frontal lobe of the macaquerain could elicit vergence eye movements, and a fur-

her animal study has demonstrated that the frontalye field is a cortical area involved in the generation ofisconjugate eye movements (Ferraina et al., 2000).

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ubsequently, Schulz and co-workers described aatient with ictal nystagmus affecting only one eye,ssociated with ictal diplopia; symptoms disappearedfter resection of right frontal focal cortical dysplasiaSchulz et al., 2013). Whereas this finding could supporthe hypothesis of an exclusively cortical involvementn monocular eye movement control, as previouslyuggested (Thurtell et al., 2009), the presence ofonocular nystagmus and spasm of the contralateral

ye observed on interictal neuro-ophthalmologicalxamination “argue for an irregular activation of bothhe cortical frontal eye field and the brainstem” (Schulzt al., 2013).ur patient had an initial rightward conjugate eye

eviation associated with a right posterior temporalischarge, followed by ictal disconjugate contraversive

leftward) horizontal eye deviation with convergenttrabismus resulting from adduction of the right eyeithout conjugate left eye abduction. It was difficult

o ascertain the presence of impaired awareness at theery onset of ictal strabismus in our patient. However,hen the strabismus appeared, she blinked, as if sheas initially aware of and disturbed by diplopia (buthen questioned postictally, the patient did not recall

ny symptom of double vision occurring immediatelyefore loss of consciousness). Immediately after theppearance of strabismus, she was not able to react toxternal stimuli. The ictal tachycardia, starting immedi-tely after the blink, could simply be the consequencef emotional stress and heightened adrenergic drive,ut may also represent a symptom of early involvementf the temporal and orbito-frontal cortex at seizurenset (Stefanidou et al., 2015).o baseline alterations in eye motility or brainstem

bnormality were found. It is therefore reasonable toonclude that in our patient, the ictal strabismus hadn exclusive cortical origin.he initial rightward conjugate eye deviation asso-iated with right posterior temporal rhythmic thetactivity (ipsiversive eye deviation) is likely to be thelinical manifestation of a seizure originating from thenferio-posterior temporal lobe (seizure onset zone)Zhang et al., 2017). MRI confirmed the presence of anpileptogenic lesion (Lüders et al., 2006) in that region,howing cortical dysplasia in the posterior section ofhe right temporal lobe. Due to the low spatial resolu-ion of scalp EEG, we could not identify with precisionhe symptomatogenic zone underlying ictal strabis-

us. Ictal activity was not recorded invasively, hence

Epileptic Disord, Vol. 20, No. 4, August 2018

t is impossible to draw definitive conclusions regard-ng possible propagation of epileptic activity from theight inferio-posterior temporal to ipsilateral frontalobe. It is possible that the epileptic activity remainednitially confined to the right temporal lobe and cor-ical regions nearby. If so, cortical regions involvedn controlling versive and vergence eye movements,

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uch as the parietal eye field and dorsolateral pre-rontal cortex (Coubard and Kapoula, 2006), or thenvolvement of middle temporal and medial superioremporal areas, which control normal smooth pursuit

ovement (Tijssen et al., 1992), may have contributedo the ictal strabismus.owever, the patient eventually had a leftward head

ersion, indicating epileptic activation of the frontalye field (inferior/medial frontal gyrus) (Bonelli et al.,007; Noachtar and Arnold, 2008). Hence, the ictal stra-ismus might have been the clinical expression ofpileptic activity involving the right frontal eye fieldsymptomatogenic zone) (Thurtell et al., 2009; Schulzt al., 2013), as further supported by the concomitantppearance of rhythmic theta activity over the rightronto-central region and by the perfusion sequenceshowing focal cortical-subcortical cerebral blood flowncrease in the right frontal eye field area, correlating

ith the ictal epileptic activity. �

cknowledgements and disclosures.e are grateful to Andrea Orioli for graphical support.o funding was received related to the preparation of this arti-

le. Francesco Brigo has received speakers’ honoraria from Eisaind PeerVoice, payment for consultancy from Eisai, and travelupport from Eisai, ITALFARMACO, and UCB Pharma. The othero-authors have no conflict of interest to declare.

Legend for video sequence

00:09. The patient has a rightward horizontal con-jugate eye deviation; the EEG shows rhythmic thetaactivity over the right posterior temporal region.00:14. Appearance of convergent strabismus due toadduction of the right eye without conjugate lefteye abduction; the EEG shows rhythmic epilepticactivity over the right fronto-central regions.00:15. The patient blinks (see blink artefact overfrontal regions).00:32. Leftward deviation (version) of the headand subsequent bilateral tonic-clonic seizure (notshown).Sensitivity: 10 �V; LF: 0.53 Hz; HF: 70 Hz; speed:20 sec/page.

Key words for video research onwww.epilepticdisorders.com

pileptic Disord, Vol. 20, No. 4, August 2018

Phenomenology: eye deviationLocalization: frontal eye fieldSyndrome: focal non-idiopathic frontal (FLE)Aetiology: dysplasia (architectural)

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Epileptic ictal strabismus

eferences

onelli SB, Lurger S, Zimprich F, Stogmann E, Assem-Hilger E,aumgartner C. Clinical seizure lateralization in frontal lobepilepsy. Epilepsia 2007; 48: 517-23.

oubard OA, Kapoula Z. Dorsolateral prefrontal cortex pre-ents short-latency saccade and vergence: a TMS study.ereb Cortex 2006; 16: 425-36.

erraina S, Paré M, Wurtz RH. Disparity sensitivity of frontalye field neurons. J Neurophysiol 2000; 83: 625-9.

alimberti CA, Versino M, Sartori I, Manni R, Martelli, Tartara A. Epileptic skew deviation. Neurology 1998; 50:469-72.

usek-Schneider GC, Uberall MA, Wenzel D. Intermittentsotropia as equivalent of absence in epilepsy. J Pediatr Oph-halmol Strabismus 2000; 37: 363-4.

ampel RS. Convergence, divergence, pupillary reactionsnd accommodation of the eyes from faradic stimula-ion of the macaque brain. J Comp Neurol 1960; 115:71-99.

üders HO, Najm I, Nair D, Widdess-Walsh P, Bingman W.he epileptogenic zone: general principles. Epileptic Disord006; 8: S1-9.

oachtar S, Arnold S. Simple motor seizures: localizing andateralizing value. In: Textbook of Epilepsy Surgery. Lüders

O. London: Informa UK Ltd, 2008.

asmussen T, Penfield W. Movement of head and eyes fromtimulation of the human frontal cortex. Res Nerv Ment Disroc 1948; 27: 346-61.

chulz R, Tomka-Hoffmeister M, Woermann FG, et al. Epilep-ic monocular nystagmus and ictal diplopia as cortical andubcortical dysfunction. Epilepsy Behav Case Rep 2013; 1:9-91.

mith WK. The frontal eye fields. In: The Precentral Motorortex. Bucy PC. Urbana, IL: University of Illinois Press, 1944.

tefanidou M, Carlson C, Friedman D. The relation-hip between seizure onset zone and ictal tachycardia:n intracranial EEG study. Clin Neurophysiol 2015; 126:255-60.

hurtell MJ, Mohamed A, Lüders HO, Leigh RJ. Evi-ence for three-dimensional cortical control of gaze frompileptic patients. J Neurol Neurosurg Psychiatry 2009; 80:83-5.

ijssen CC, Kort PLM, Bastiaensen LAK, Voskuil PHA. Epilep-ic eye deviation and nystagmus. Clin Neurol Neurosurg992; 94: 77.

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nd epileptic eye deviation. Can J Ophthalmol 1996; 31:69-72.

hang W, Liu X, Zuo L, Guo Q, Chen Q, Wang Y. Ipsiversivectal eye deviation in inferioposterior temporal lobe epilepsy-wo SEEG cases report. BMC Neurol 2017; 17: 38.

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TEST YOURSELFEDUCATION

(1) What does ictal strabismus suggest?A. Subcortical involvement in monocular eye movement controlB. Cortical involvement in monocular eye movement controlC. Involvement of the cerebellum in monocular eye movement control

(2) Ictal strabismus:A. always originates from parieto-occipital regionsB. is an exclusively subcortical phenomenonC. is a heterogeneous epileptic phenomenon, which may arise from activity involving the frontal eye field orother cortical regions involved in controlling versive and vergence eye movements

(3) Ipsiversive conjugate eye deviationA. has been reported in seizures originating from the inferio-posterior temporal lobeB. is the consequence of epileptic activity involving the frontal eye fieldC. is constantly associated with good response to antiepileptic drugs

Note: Reading the manuscript provides an answer to all questions. Correct answers may be accessed on thewebsite, www.epilepticdisorders.com, under the section “The EpiCentre”.