Juvenile idiopathic epilepsy (JIE) is categorized as a generalized epilepsy. Epilepsy classification entails electrocortical characterization and localization of epileptic discharges (ED) using electroencephalography (EEG).

Hypothesis/Objectives

Characterize epilepsy in Egyptian Arabian foals with JIE using EEG.

Animals

Sixty-nine foals (JIE, 48; controls, 21).

Methods

Retrospective study. Inclusion criteria consisted of Egyptian Arabian foals: (1) JIE group diagnosed based on witnessed or recorded seizures, and neurological and EEG findings, and (2) control group of healthy nonepileptic age-matched foals. Clinical data were obtained in 48 foals. Electroencephalography with photic stimulation was performed under standing sedation in 37 JIE foals and 21 controls.

Results

Abnormalities on EEG were found in 95% of epileptic foals (35 of 37) and in 3 of 21 control asymptomatic foals with affected siblings. Focal ED were detected predominantly in the central vertex with diffusion into the centroparietal or frontocentral regions (n = 35). Generalization of ED occurred in 14 JIE foals. Epileptic discharges commonly were seen during wakefulness (n = 27/37 JIE foals) and sedated sleep (n = 35/37 JIE foals; 3/21 controls). Photic stimulation triggered focal central ED in 15 of 21 JIE foals.

Conclusions and Clinical Importance

Juvenile idiopathic epilepsy has a focal onset of ED at the central vertex with spread resulting in clinical generalized tonic-clonic seizures with facial motor activity and loss of consciousness. Electroencephalography with photic stimulation contributes to accurate phenotyping of epilepsy. Foals with this benign self-limiting disorder might serve as a naturally occurring animal model for self-limited epilepsy in children.

Abbreviations

BRE: benign rolandic epilepsy
ED: epileptic discharges
EEG: electroencephalogram
EEG: electroencephalography
IED: interictal epileptic discharges
IPS: intermittent photic stimulation
JIE: juvenile idiopathic epilepsy
PD: photic driving
PPR: photoparoxysmal response
PS: photic stimulation
SeLECTs: self-limited epilepsy with centrotemporal spikes
SWS: slow wave sleep

1 INTRODUCTION

Seizures and epilepsy are relatively uncommon in horses compared to other species, and limited information is available on their etiology.¹ Juvenile idiopathic epilepsy (JIE) is the only well-characterized large animal epileptic disorder based on clinical, neurologic, electroencephalography (EEG), and histopathological examination.² Currently, a single comprehensive report describes the semiology of disease and EEG data in foals with JIE.² Revision of current electroclinical data in properly phenotyped foals based on documented clinical observations and standard EEG protocol performed by neurologists is needed.³ Juvenile idiopathic epilepsy has been described in Egyptian Arabian foals with an onset ranging from 2 days to 6 months of age (median, 2 months), with apparent resolution and no short- or long-term sequelae by 1 to 2 years of age.² Thus far, no sex or coat color predilection has been reported in affected foals, and no apparent precipitating events or underlying disease has been identified.²

Juvenile idiopathic epilepsy is manifested as observable sudden generalized tonic-clonic seizures with loss of consciousness with no apparent preictal signs.² Cortical blindness, disorientation, obtundation, alterations in behavior, dysphagia, and abnormal gait are common postictal signs.² Cortical blindness is the most common postictal sign and can last from a few minutes to weeks with vision returning within 24 hours in most foals (MA, personal communication).² Affected foals are clinically and neurologically normal during the interictal period.² In terms of survival, the prognosis for life and physical activity is good as long as complications such as trauma of the head and other body parts, corneal ulceration, and aspiration pneumonia are prevented or treated properly.²

To define, classify, advance understanding of pathophysiology, and improve therapeutic management of epileptic disorders in veterinary medicine as in the case of human medicine, electroencephalography is an essential diagnostic modality for the complete evaluation of patients with epilepsy.^{4, 5} Like some epileptic syndromes in infants, JIE has a familial basis and is suspected to be inherited in an autosomal dominant manner with a self-limiting pattern.^{2, 6, 7} Attempts at identifying a possible genetic cause of JIE in foals have been made.^8-11 Accurate definition of phenotype must include EEG data obtained and interpreted by trained neurologist specialized in the investigation of epileptic disorders with suspected underlying genetic cause.¹² Juvenile idiopathic epilepsy has been described and reported as a generalized epilepsy based on clinical manifestations.² However, proper classification of epileptic syndromes as described in human medicine is based not only on seizure semiology, but also on the origin of epileptic discharges (ED) upon EEG examination.^{4, 5} Therefore, our objective was to revise and classify epilepsy in Egyptian Arabian foals with JIE according to classification guidelines used in humans.⁵ Clinical and EEG data obtained using a standardized EEG protocol for equine species under standing sedation were reviewed.^{2, 3, 13, 14}

2 MATERIALS AND METHODS

2.1 Foals

Ours was an observational retrospective case-control study. Review and reclassification of epilepsy was done based on clinical and EEG data from 2 institutions: The William R. Pritchard Veterinary Medical Teaching Hospital and the Equine and Comparative Neurology Research Group at the University of California Davis (UCD), and the Equine Veterinary Medical Center (EVMC) in Doha, Qatar. To be included in the study, foals had to be of Egyptian Arabian breed and lineage with a history of witnessed or video-recorded seizures or EEG evidence of ED reviewed by a neurologist. Clinically healthy age matched Egyptian Arabian foals with no history of seizures were selected as controls. The electronic data base from UCD (1995-2023) was searched using the words seizures, epilepsy, convulsions, paroxysms, photic stimulation, electroencephalography, and EEG. Physical and neurological examinations were performed before each EEG study by board-certified large animal internal medicine specialists. Most foals from UCD were examined by a board-certified veterinarian neurologist who also performed EEG evaluation. Medical and EEG records from healthy nonepileptic Egyptian Arabian foals within 1 year of age also were retrieved from both institutions and considered as controls. The protocol was approved by the Institutional Animal Care and Use Committee of UCD (#21858) and the EVMC (#2021-1179) and client consent was obtained.

2.2 Sedation protocol

Each foal was placed in a large, padded stall with its mare and gently physically restrained by a halter (a nonharmful routine restraint device approved for horses). Foals from UCD were sedated using IV xylazine hydrochloride (Anased LA 100 mg/mL, VetOne, MWI, Boise, ID, USA) at a dosage of 0.5 to 1 mg/kg for foals <2 months of age, and detomidine hydrochloride (Dormosedan 10 mg/mL, Zoetis, Parsippany, NJ, USA) at a dosage of 0.01 mg/kg for foals ≥2 months of age for placement of SC needle electrodes and video EEG recording. Foals from the EVMC were sedated using sublingual detomidine hydrochloride (Dormosedan gel 3 mL, 7.6 mg/mL, Zoetis, Parsippany, NJ, USA) at a dosage of 0.08 mg/kg, followed by topical lidocaine cream (Xylocream: 2.5% lidocaine and 2.5% of prilocaine, 30 g, Verisfield, Chalandri, Greece) on the scalp at predetermined areas for electrodes placement according to UCD EEG protocol for equine species.^{2, 3, 13, 14}

2.3 Electroencephalogram

All EEG studies were performed under standing sedation as described and consisted of an electroencephalogram, electrooculogram (EOG), ECG, and respiratory monitoring. At UCD, 2 EEG machines were used depending upon availability: (1) Nihon Kohden (Neurofax 2110, Nihon Kohden America Inc, Foothill Ranch, CA, USA) with integrated photostimulator and video and (2) Nihon Kohden digital wireless EEG system (Neurofax Wireless Input 1000A, Nihon Kohden America Inc, Foothill Ranch, CA, USA) with integrated video. At the EVMC, a Nicolet NicOne digital EEG system (Natus Medical Inc, Middleton, WI, USA) with integrated photostimulator and video was used for recording. Electrode nomenclature and placement were based on a modified 10-20 system used in humans and described in horses (Figure 1A).^{2, 3, 13} Number designation followed the EEG protocol used in humans with even and odd numbers denoting right and left side, respectively, and vertex denoted as “z.” Disposable SC needle electrodes (UCD: Grass/Astro-Med, West Warwick, RI, USA; EVMC: Neurodart, 0.40 × 13 mm, 250 cm cable, DIN4802, Color set B, SPES Medica, Genoa, Italy) were previously labeled with stickers as follows: Z = ground (1 electrode), FP = frontal polar (2: FP1, FP2), F = frontal (3: F3, Fz, F4), C = central (3: C3, Cz, C4), P = parietal (3: P3, Pz, P4) and O = occipital (2: O1, O2) regions, A = auricular (1 on each ear at its base: A1, A2), OD = right eye (1), and OS = left eye (1). The electrodes were placed SC in the scalp located at an equal distance of approximately 2 cm from each other in cranial to caudal and transverse directions as per UCD EEG protocol.¹³

Details are in the caption following the image — **FIGURE 1**
Open in figure viewer PowerPoint

EEG electrode placement and montage. (A) UCD protocol for equine EEG. Diagram displaying origin of ED at central vertex (Cz, circle). (B) Wake tracing (Bipolar montage) illustrating focal interictal discharges with phase reversal at Cz (dashed box). (C) Average montage showing maximum electronegativity at Cz (asterisk) with involvement to adjacent cortical regions. ECG, electrocardiogram; EOG, electro-oculogram. Calibration bar shown at bottom right corner of figures representing 1 second for time and sensitivity of 70 microvolts (μV).

Bipolar (rostral to caudal and transverse) and average montages were used (Figure 1B,C). The impedance was checked at the beginning of each recording to ensure interelectrode impedances were <10 kΩ to minimize obscuration of the tracing by artifacts. Movement artifacts were recorded when noted with the aid of the video recording. Electroencephalographic recording ranged from 40 to 50 minutes and included 20 to 30 minutes of sleep achieved through sedation, followed by periods of drowsiness and wakefulness at the end of the study. Being prey animals, foals can achieve slow wave sleep (SWS) while standing because of their well-adapted musculoskeletal stay apparatus. Slow wave sleep was determined by the presence of background slowing (delta activity), vertex sharp waves, sleep spindles, K-complexes or some combination of these. Paroxysms in support of ED consisted of spikes (duration <70 ms), sharp waves (duration 70-200 ms), spike and wave discharges, or multiple spike complexes. Epileptic discharges were classified as focal (if originating from a localized focus), multifocal (if involving ≥3 independent foci involving both hemispheres) or generalized (if involving all electrode channels simultaneously). Electroencephalographic recordings were reviewed by a veterinary neurologist (MA) and a human medical neurologist (RB). Foals' clinical status was not blinded to the examiners because foals were presented and evaluated for seizures at our institutions.

2.3.1 Activation procedures

Activation procedures performed during the end of EEG recordings (during wakefulness) included intermittent photic stimulation (IPS), sound stimulation, and hyperventilation. Intermittent photic stimulation was performed using the following frequencies: (1) UCD: 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, and 30 Hz; and (2) EVMC: 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 50, and 60 Hz. Sound stimulation consisted of an intermittent loud clap. When photoparoxysmal responses (PPR) were recorded at a particular frequency, photic stimulation (PS) at that frequency was repeated to ensure reproducibility. Hyperventilation was induced by using a plastic rebreathing bag for 1 minute. Once the recording was completed, electrodes were gently removed, and the scalp was cleaned with alcohol.

3 RESULTS

3.1 Foals

Based on history of seizures and physical and neurological examinations, 48 Egyptian Arabian foals were classified as JIE and 21 foals as nonepileptic controls. The sex distribution of JIE foals included 25 fillies and 23 colts. The median age was 2 months with a range of 2 days to 9 months old. Only 2 neonatal foals (2 and 3 days old, respectively) with no concurrent or underlying disease were diagnosed with JIE. The age distribution based on sex consisted of a median of 2 months for fillies (range, 2 days to 9 months) and 3 months for colts (range, 15 days to 8 months; Table 1). Historically, 32 of 48 foals with JIE had affected siblings, 5 had no affected siblings, and in 11 foals it was unknown. No coat color predisposition was apparent (Table 1). The nonepileptic group consisted of 21 foals: 12 colts and 9 fillies with a median age of 3.5 months (range, 2-12 months old; Table 1). Fifteen of these foals did not have affected siblings, and 6 had affected siblings.

TABLE 1. Summary of signalment, clinical and epilepsy characteristics in JIE and control foals.

	JIE (n = 48)	Control (n = 21)
Age
Median (range)	2 m (2 d to 9 m)	3.5 m (2 m to 12 m)
Sex
Male	23 (48%)	12 (55%)
Female	25 (52%)	9 (45%)
Color
Bay	18 (37.5%)	6 (28%)
Chestnut	12 (25%)	5 (24%)
Gray	18 (37.5%)	10 (48%)
Affected siblings with JIE
Yes	34 (71%)	6 (29%)
No	5 (10%)	15 (71%)
Unknown	9 (19%)	0
Epilepsy characteristics
Median (range) age at onset	2 m (2 d to 9 m)	NA
Seizure type
Focal	4 (8%)	NA
Generalized	41 (86%)	NA
Focal + generalized	0	NA
Undetermined	3 (6%)	NA
Antiseizure medication
Monotherapy	37 (77%)	NA
Polytherapy (≥2)	7 (15%)	NA
No therapy	4 (8%)	NA
Response to treatment	(n = 44)
Yes	39 (89%)	NA
No	3 (6%)	NA
Not reported	2 (5%)	NA

Abbreviations: d, days; m, months; NA, not applicable.

Clinically, 41 of 48 JIE foals had generalized seizures, 4 had focal seizures, and in 3 the onset was unknown but the foals displayed postictal signs such as cortical blindness, obtundation, tongue paresis, and ataxia (Table 1). Seizures were characterized as violent generalized tonic-clonic with a facial motor component, trismus, and loss of consciousness. Focal seizures consisted of facial motor alterations including trismus, chewing, and tongue paresis resulting in protrusion. In foals in which duration of seizures was recorded, seizures lasted from 20 seconds to 2 minutes with seizures in 65% of the foals lasting <1 minute. Only in 1 foal was the seizure prolonged, lasting 5 minutes. Postictal signs included disorientation, obtundation, cortical blindness, mydriasis, decreased palpebral reflex, lack of suckle reflex, dysphagia, tongue protrusion, proprioceptive deficits of all limbs, and ataxia. Duration of postictal signs varied from a few minutes to days with cortical blindness lasting the longest from a few minutes to weeks. Otherwise, foals were neurologically normal in the interictal period.

Antiseizure medication was used in the majority of foals (44/48 JIE foals) for a few months (median, 6 months; range, 2.5-9 months) and their response is shown in Table 1. In brief, most foals responded to monotherapy consisting of phenobarbital (n = 28), levetiracetam (n = 8), or gabapentin (n = 1). Multidrug combinations for seizure control were required in a subset of foals and consisted of phenobarbital/levetiracetam (n = 4) and phenobarbital/potassium bromide (n = 3). Six foals were not on antiseizure drugs as elected by the owner because of the low frequency of seizures and cost. Adequate response to treatment was defined as absence or decreased frequency of seizures in 39 of 44 foals. Three nonresponders were receiving monotherapy with phenobarbital (n = 2) or levetiracetam (n = 1). Common seizure-related complications included generalized body trauma (n = 21) including rib fractures in 3 foals and vertebral column fracture in 1 foal, head trauma (n = 16) that in 1 case resulted in multiple comminuted skull fractures, dysphagia resulting in aspiration pneumonia (n = 13), and corneal ulceration (n = 6).

3.2 Electroencephalogram

Electroencephalography was performed in 37 of 48 JIE foals and in all 21 control foals (nonepileptic; Table 2). The majority of JIE foals (n = 33/37) had been tapered off antiseizure medications days to weeks before and were not on long term antiseizure medication at the time of the EEG study. The data obtained were thoroughly examined including EEG tracings and simultaneous video recording for each foal under study. The EEG study included recording during states of wakefulness, sedated drowsiness and sleep (Figures 2 and 3). None of the foals lay down during SWS. During sleep, the background consisted predominantly of intermittent 3-4 Hz delta activity of SWS. Vertex sharp waves, sleep spindles, and rarely K-complexes were observed during this phase. Second degree atrioventricular block was observed in 31 of 37 foals during SWS. Heart and respiratory rates decreased during SWS.

TABLE 2. Summary of EEG findings in JIE and control foals.

	JIE (n = 37)	Control (n = 21)
EEG abnormalities
Present	35 (95%)	3 (14%)
Absent	2 (5%)	18 (86%)
Affected siblings with JIE
Yes	27 (73%)	6 (29%)
No	4 (11%)	15 (71%)
Unknown	6 (11%)	0
ED localization	(n = 35)	(n = 3)
Focal	35 (100%)	3 (100%)
Multifocal	0	0
Generalized	0	0
Secondary generalization	14 (40%)	0
Photic stimulation	(n = 21)	(n = 21)
Normal	(n = 6/21 [29%])	(n = 19/21 [90%])
Photic driving (PD)	4 (19%)	13 (62%)
No response	2 (9.5%)	6 (28%)
Abnormal	(n = 15/21 [71%])	(n = 2/21 [10%])
Photoparoxysmal responses (PPR)	13 (62%)	1 (5%)
PD + PPR	2 (9.5%)	1 (5%)

Note: EEG recordings done in 37 of 48 JIE foals and 21 controls.

3.2.1 Interictal epileptic paroxysms

Of 37 EEG recordings in JIE foals, interictal epileptic discharges (IED) were noted in 95% of cases (n = 35/37) in the form of focal spike-and-wave discharges (n = 21 foals) or focal spikes with secondary generalization (n = 14 foals; Table 2). Focal IED were the most common EEG finding (n = 35/37), characterized by spikes or sharp waves seen with maximum electronegativity at the central vertex (Cz) with spread into the left or right centroparietal regions (Table 2, Figures 2 and 3), and less frequently into the frontocentral regions in 4 foals. Interictal epileptic discharges were seen predominantly during sleep (n = 35/35) but also during wakefulness in 27 JIE foals. Because of the short duration of the EEG studies, ictal recordings were obtained only in 2 foals and demonstrated a focal ictal onset at Cz with subsequent secondary generalized spread. Figure 1 depicts focal onset at central vertex, and Figures 2 and 3 depict bilaterally simultaneous generalized discharges in JIE foals. Most control foals (18 of 21) had normal electroencephalograms with absence of IED. In 3 control foals, focal spike and waves discharges occasionally were observed in the frontocentral region (Table 2). None of these 3 control foals had a history of epilepsy, but all had a family history of a sibling with JIE.

3.2.2 Activation procedures

Auditory stimulation using a loud clap elicited a movement artifact from a reflex head movement but did not result in any electrographic changes on the EEG tracing in JIE (n = 37/37) or control (n = 21/21) foals. Intermittent PS resulted in photoparoxysmal responses in the form of ED in the central or centroparietal regions in 62% (n = 13/21) of JIE foals (Figure 4) versus in 10% (n = 2/21) of control foals. None of these responses were associated with any clinical signs while recording. Furthermore, all of the photoparoxysmal responses were reproducible and time-limited to the duration of PS and as such were not self-sustaining. Normal photic driving (PD) in the occipital regions was observed more frequently in control foals (n = 19/21) as opposed to JIE foals (n = 6/21). Hyperventilation was performed in 11 JIE foals and did not trigger ED or any change to the background recording. However, it did result in movement artifacts.

4 DISCUSSION

We comprehensively reviewed and reported information in a large number of Egyptian Arabian foals with JIE based on proper and strict phenotyping including EEG evaluation with activation procedures performed and interpreted by neurologists in human and veterinary medicine. Doing so is the first essential step for accurate genotyping studies. Our study confirms that epilepsy in Egyptian Arabian foals with JIE indeed has a focal onset of ED in the central vertex with rapid spread to other cortical areas of the brain resulting in generalized seizures. This conclusion is supported by findings from interictal EEG recordings that consistently demonstrated the presence of focal ED in the central regions in foals with JIE. Generalized spread of ED from focal origin was observed in 40% of the foals while recording EEG during the interictal period, which in 2 foals resulted in clinical generalized tonic-clonic seizures and loss of consciousness while recording. Epileptic discharges were recorded in states of wakefulness (77%) and sleep (100%). Photic stimulation induced a photic response in 91% of JIE foals with 79% triggering ED, and 21% PD. Other activation procedures such as auditory stimuli and hyperventilation did not induce ED. Generalized tonic-clonic seizures and loss of consciousness were the most common clinical manifestations in foals (91%) with witnessed or video-recorded seizures. Focal facial, oral, and tongue motor seizures were observed in 4 foals and, in 3 foals with postictal signs, had an unknown onset.

Interictal EEG examination was useful to identify ED in 3 colts with no apparent history of seizures and emphasizes the importance of performing EEG studies for the correct definition of phenotype for future genotype studies. However, despite an abnormal EEG denoting a lowered seizure threshold, these foals cannot be classified as being epileptic, nor are antiseizure medications indicated in this situation. Interestingly, these colts had a family history of siblings with JIE, suggesting that epilepsy in Egyptian Arabian foals is likely inherited with incomplete penetrance and that EEG abnormalities might be inherited without the development of seizures. A similar situation has been described in the human medical literature where the prevalence of EEG abnormalities in asymptomatic siblings of patients with childhood epilepsy syndromes far exceeds that seen in the general population, indicating a genetic susceptibility to the inheritance of hyperexcitable neuronal networks.¹⁵ In contrast, 89% of JIE foals with recorded family information had affected siblings. It is important to note that absence of interictal EEG abnormalities does not rule out epilepsy as in the case of 2 foals with JIE in our study, and cases could be misclassified as nonepileptics.

Standing sedation (IV and sublingual) and EEG protocols used in our study allowed us to obtain interpretable data with minimal movement artifacts and uneventful recovery. In order to investigate various states of vigilance (arousal and sleep) and prevent alteration of EEG activity including obliteration of ED and cause burst suppression, it is important to avoid general anesthesia when possible when performing EEG studies.^{16, 17} Previously, successful use of α2-adrenergic agonists has been reported to perform EEG studies under standing sedation in foals and adults.^{2, 3, 14} These studies reported 2 different sedation protocols using IV or sublingual α2-adrenergic agonists that provided an excellent plane of sedation for EEG. A further advantage of using α2-adrenergic agonists in horses is the induction of SWS without altering the yield of the EEG findings.¹⁴ Specific stages of sleep are known to facilitate epileptic activity and seizures in humans and might explain why ED were seen in all of our foals during states of sleep.^{18, 19} Indeed, yield of ED during sleep in our foals appeared to be higher than the 30% to 40% reported yield in humans.¹⁹ Second degree atrioventricular block is a common finding during SWS in horses and also was observed in 80% of our foals during this state.¹³ Atrioventricular block might result from an increase in parasympathetic drive resulting in decreased cardiac activity as reported in humans during this stage of sleep.²⁰ Furthermore, detomidine hydrochloride is known for its cardiovascular effects which include occurrence of atrioventricular block.^{21, 22} The addition of topical lidocaine hydrochloride to the scalp facilitated painless needle insertion and did not interfere with EEG recording.

The Epilepsy Foundation (www.epilepsyfoundation.org.au, December 5, 2022) divides seizure semiology into various phases. According to this definition, preictal signs were not apparent in these foals whereas the ictal phase consisted of sudden violent generalized tonic-clonic seizures with loss of consciousness and focal facial and tongue motor seizures in 91% and 9% of the foals, respectively. The postictal phase consisted of disorientation, obtundation, cortical blindness, dysphagia, tongue paresis, proprioceptive deficits, and ataxia. Based on clinical manifestations, seizures in these foals were classified as generalized tonic-clonic as previously described.² However, according to the classification of epilepsy and seizures in humans, seizures were reclassified in these foals based on their electroencephalographic origin.^{4, 5, 23} Seizures in these foals originated in the vertex centroparietal region, and therefore are considered a focal onset epilepsy.^{2, 23} Abnormal activity can spread from its origin to other regions of the brain as observed in these foals. Generalized spread of ED resulted in clinical seizures in 2 foals while recording their EEG. Our study also emphasizes 2 important facts: (1) abnormal EEG activity can occur during the interictal phase as seen in 95% of the foals in our study, and (2) lack of ED during the recording does not rule out epilepsy and longer or serial recordings might be necessary to further investigate electrocortical status.

Juvenile idiopathic epilepsy has similarities to self-limited epilepsy with centrotemporal spikes (SeLECTs), previously known as benign Rolandic epilepsy (BRE), which is the most common epilepsy in children, constituting 15% of childhood epilepsy cases.^{6, 24} The similarities include early onset (1-4 years of age), self-limited with complete remission by age 15 years (hence benign), and no apparent sequelae in children.²⁴ Rolandic epilepsy is so termed because the origin of ED is at the rolandic area of the brain which consists of the centrotemporal area (centroparietal in foals) around the central sulcus of the brain.^24-26 The Rolandic area controls facial, oropharynx, and tongue function, which explains the clinical manifestations in children with SeLECTs.²⁴ Because of the anatomy and shape of the horse's head, EEG recording from the temporal region is not possible and parietal recording is the closest to this region. Clinical manifestations in children tend to occur infrequently, most often at night, usually lasting <2 minutes, and involve seizures of the face, oropharynx, and tongue resulting in twitching, numbness or tingling of the face and tongue, interference with speech, and drooling.²⁴ Seizures can spread and become generalized occurring more frequently at night (www.epilepsyfoundation.org.au, December 5, 2022).^{24, 26} Similarly, seizures in these foals lasted <2 minutes, and foals with focal seizures manifested motor alterations involving the face, mouth, and tongue. Furthermore, foals with generalized seizures often had trismus, wide-open mouth, or chewing movements.

Self-limited epilepsy with centrotemporal spikes is classified as genetic and suspected to have a dominant mode of inheritance affecting girls and boys, but more often boys.²⁴ Juvenile idiopathic epilepsy is suspected to be a genetic epilepsy with a dominant mode of inheritance based on pedigree analysis in which a sex predilection has not been noted.^{2, 8} Furthermore, EEG of asymptomatic first relatives of patients with SeLECTs has been reported to show ED,¹⁵ which also was observed in our study in 2 asymptomatic foals with affected siblings. Like children with SeLECTs, JIE also has been called benign juvenile epilepsy because of its spontaneous resolution.^{2, 27} The use of animal models to investigate the underlying etiology and mechanisms of pediatric epileptic syndromes is mostly limited to experimentally-engineered or induced models.²⁸ Therefore, based on similarities such as being a self-limiting (benign) disorder with an early onset of seizures, seizure semiology, and EEG findings, foals with JIE might serve as a naturally occurring animal model for SeLECTs. However, foals with JIE most commonly display sudden violent generalized tonic-clonic seizures with loss of consciousness in contrast to children who mainly manifest focal facial motor seizures.^{2, 29} Less commonly, focal seizures in foals involved the face, oropharynx, and tongue similar to children with SeLECTs.²⁹ Furthermore, most foals with JIE independent of generalized or focal seizures had postictal facial, oropharynx, and tongue dysfunction resulting in dysphagia.

Activation procedures for the investigation of epilepsy during EEG recording used in our study included PS, sound, and hyperventilation.^{2, 30, 31} No alterations of EEG activity were observed upon sound stimulation or hyperventilation. Photic stimulation is widely used in routine EEG to aid in the diagnosis of epilepsy in humans.³⁰ In our study, photic responses such as ED, PD, and combination of ED and PD were commonly identified. More importantly, all triggered ED in these foals occurred in the centralparietal region upon PS. Photic driving as observed in these foals also can be observed in normal foals and not considered pathological.³ Photic driving is a physiological rhythmic activity representing repetitive visual evoked potentials produced over the occipital region time-locked in response to a photic flash.³²

Limitations of our study included the lack of ictal recordings. However, such recording was precluded because of safety concerns and the unpredictability of epileptic episodes. Lack of ED does not rule out epilepsy as shown in 2 foals with JIE. Longer duration or repeated EEG recordings might aid in ED identification. Horse head anatomy and increased likelihood of movement artifacts (eg, highly movable ears) at the location of the temporal region, prevented EEG recording from that location. Furthermore, clinicians were not blinded to the clinical status of the foals examined because foals were presented for seizures.

5 CONCLUSION

Our study reevaluated epilepsy in Egyptian Arabian foals with JIE and determined a focal onset of ED in the central vertex with spread to other cortical regions of the brain resulting in sudden violent generalized tonic-clonic seizures with loss of consciousness (more common) or focal facial (including mouth and tongue) seizures (less common). Epileptic discharges were seen during wakefulness and sleep but predominantly during sleep, which α2-adrenergic agonists promote in equine species. Epileptic discharges were triggered in most foals with PS. Juvenile idiopathic epilepsy appears to be inherited as a dominant autosomal trait likely with incomplete penetrance resulting in some asymptomatic foals (siblings of affected foals) based on the presence of ED upon EEG examination. We concluded that EEG is crucial to identify and classify epilepsy correctly in foals with JIE and constitutes the basis for accurate future genetic studies. Furthermore, foals with JIE might serve as a naturally occurring animal model of SeLECTs in children because of similarities in seizure semiology.

ACKNOWLEDGMENT

This work was supported by gifts to the Equine and Comparative Neurology Research Group #V435AM2 at University of California, Davis (Aleman), the Equine Veterinary Medical Center-Member of Qatar Foundation (RG22_TV1), and Sidra Medicine, Doha, Qatar. The authors thank the clinicians and staff from the William R. Pritchard Veterinary Medical Teaching Hospital at the University of California Davis, and the Equine Veterinary Medical Center at Doha, and Sidra Medicine at Doha, Qatar.

CONFLICT OF INTEREST DECLARATION

Authors declare no conflict of interest. Dr. Vinardell's current employer had no influence on this study.

OFF-LABEL ANTIMICROBIAL DECLARATION

Authors declare no off-label use of antimicrobials.

INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC) OR OTHER APPROVAL DECLARATION

Approved by University of California, Davis IACUC #21858, EVMC #2021-1179.

HUMAN ETHICS APPROVAL DECLARATION

Authors declare human ethics approval was not needed for this study.

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Volume38, Issue1

January/February 2024

Pages 449-459

Juvenile idiopathic epilepsy in Egyptian Arabian foals, a potential animal model of self-limited epilepsy in children