The Significance of Ear Plugging in Localization-related Epilepsy

Transcription

1 Epilepsia, 44(12): , 2003 Blackwell Publishing, Inc. C 2003 International League Against Epilepsy The Significance of Ear Plugging in Localization-related Epilepsy Dave F. Clarke, Hiroshi Otsubo, Shelly K. Weiss, Shiro Chitoku, Sylvester H. Chuang, William J. Logan, Mary-Lou Smith, Irene Elliot, Elizabeth W. Pang, James T. Rutka, and O. Carter Snead, III Department of Pediatrics, Divisions of Neurology, Neuropsychology, Diagnostic Imaging, and Division of Neurosurgery, The Hospital for Sick Children,University of Toronto,Toronto, Ontario,Canada Summary: Purpose: The localizing value of ear plugging in the treatment of auditory onset partial seizures, to our knowledge, has not been previously described. We propose that ear plugging is a clinical response to a sensory seizure manifested as an auditory hallucination and a tool for identifying the seizure focus in the auditory cortex on the superior temporal gyrus. Methods: We report on three children who had prior epilepsy surgery for recurrent symptomatic localization-related epilepsy and who, subsequent to their surgery, displayed stereotyped unilateral or bilateral ear plugging at the onset of partial seizures. We studied scalp video electroencephalography (VEEG), magnetoencephalography (MEG), and magnetic resonance imaging (MRI) in all three. Additionally, we used electrocorticography (ECoG) in two patients, intracranial VEEG monitoring in one patient, and functional MRI language mapping in two patients. Results: All three patients plugged their ears with their hands during auditory auras that localized to the superior temporal gyrus and were followed by partial seizures that spread to a wider field, as shown on scalp and intracranial VEEG. All three patients had MEG interictal discharges in the superior temporal gyrus. One patient who was nonverbal and unable to describe an auditory phenomenon plugged the ear contralateral to where temporal lobe onset seizures and MEG interictal discharges occurred. Conclusions: Ear-plugging seizures indicate an auditory aura and may also lateralize seizure onset to the contralateral temporal lobe auditory cortex. Stereotyped behaviors accompanied by epileptic seizures in children who have poor communication skills are important in the seizure semiology of localization-related epilepsy. Key Words: Ear plugging Magnetoencephalography Auditory hallucination Temporal lobe epilepsy. Heschl s gyrus, located on the dorsal surface of the superior temporal convolution and partly buried in the sylvian fissure, is the primary auditory receptive area. Stimulating the gyrus and the surrounding temporal area causes patients to hear simple sounds, such as ringing, chirping, booming, buzzing, etc. (1). Although the auditory receptive area receives input from both ears, direct stimulation of the area induces sounds contralateral to the side of stimulation (1). Ictal unformed auditory hallucinations also localize in the superior temporal neocortex and the temporal operculum (2). Ear plugging is a stereotyped behavior sometimes displayed by children with recurrent epilepsy. This behavior may precede a partial or generalized seizure and suggests a response to an auditory phenomenon. Often, learning disabilities or poor communication skills prevent children from describing these auditory auras. Accepted August 17, Address correspondence and reprint requests to Dr. H. Otsubo at Division of Neurology, Department of Pediatrics, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. hiroshi.otsubo@sickkids.ca We propose that ear plugging is the clinical response to a sensory seizure manifested as an auditory hallucination and is a tool for identifying the seizure focus in the auditory cortex on the superior temporal gyrus. We report on three children who had prior epilepsy surgery for recurrent symptomatic localization-related epilepsy and who, subsequent to their surgery, displayed stereotyped unilateral or bilateral ear plugging at the onset of partial seizures. PATIENTS AND METHODS Patients We studied three male children who had undergone surgery for recurrent epilepsy at the Hospital for Sick Children. All had auditory auras characterized by plugging their ears with their hands, followed by partial seizures. Two children were ambidextrous, and one was left-handed. We localized and lateralized the sources of epileptic discharges from scalp video-electroencephalography (VEEG) and magnetoencephalography (MEG) in three patients, from electrocorticography (ECoG) in two, and 1562

2 EAR PLUGGING IN EPILEPSY 1563 from intracranial VEEG (IVEEG) in one. We performed neuroimaging studies using magnetic resonance imaging (MRI) in three patients. In the two patients with verbal skills, we used functional MRI (fmri) in both and intracranial language mapping in one. Parents gave informed consent for their children to undergo these procedures, and our institutional review board approved the use of these procedures for the assessments in this study. EEG studies All patients underwent prolonged VEEG recordings. The digital EEG was recorded from 19 scalp electrodes placed according to the International system (BMSI 5000; Nicolet, Madison, WI, U.S.A.). Ictal recordings were obtained in all three patients. Patient 1 had extraoperative IVEEG with a subdural electrode array that was constructed based on the results of scalp EEG, MRI, and MEG. Patients 1 and 2 had intraoperative ECoG recorded with a 4 5 surface electrode array before and after resection. MRI procedures MRI studies were performed with a GE 1.5-T Signa Advantage 5.6 unit (GE Medical Systems, Milwaukee, WI, U.S.A.). We used volumetric images in the axial plane that were produced by a three-dimensional, T 1 -weighted image sequence. We also used axial T 2 -weighted images. fmri procedures We instructed the patients to name covertly a line drawing from the Boston Naming Test (object naming), read a word (word reading), or generate a semantically related verb for a concrete noun (verb generation). We performed fmri while the patients carried out these tasks. We calculated a composite activation image from the mean signal intensity of six images for each task and a composite resting image from the mean signal intensity of the six individual resting images. We superimposed significantly different (p < 0.05) pixel locations on highresolution MRI images. Simultaneous MEG and EEG recording We performed MEG studies by using a whole-head Omega 151-channel gradiometer system (CTF, Port Coquitalam, BC, Canada). We recorded 15 data sets of spontaneous MEG and EEG lasting 2 min in a magnetically shielded room. We used a single moving dipole in a spherical head model to localize one equivalent current dipole source for each epileptic spike. We obtained three fiducial points (right and left preauricular and nasion) for coregistration of MEG and the thin-sliced T 1 -weighted MR images. MEG auditory evoked response recording Subsequent to the MEG/EEG recording, MEG auditory evoked responses were recorded. Each child listened to monaurally presented 1-kHz tones through plastic ear inserts with contralateral white noise. Both ears were tested. The recording underwent signal averaging, and the resultant response was localized to temporal auditory cortex by using an equivalent current dipole source method. Language mapping procedures In patient 1, we mapped language areas by stimulating with subdural grids during tasks targeted to assess expressive speech. We used data from fmri to select tasks thought to be maximally excitatory to the sensitive cortical areas. We started electrical stimulation only after the child had successfully responded to several tasks, including picture naming, color naming, and counting. Stimulation was terminated after 20 s. We confirmed any interrupted speech by repeating electrical stimulation of the same site. CASE REPORTS Patient 1 This 8-year-old ambidextrous boy had a history of temporal lobe tumor, developmental delay, and localizationrelated epilepsy. His seizure onset occurred at age 3 years. In his initial seizures, he often plugged his ears and changed his facial expression to a strange look before the evolution of seizures. The seizures consisted of motion arrest, staring, a sudden head drop, and tonic posturing of both upper extremities, lasting s. MRI revealed a cystic lesion with possible surrounding cortical dysplasia in the left temporal lobe. At age 5 years, he underwent cortical resection of a left temporal dysembryoplastic neuroepithelial tumor (DNET) and cortical dysplasia. Surgery also included multiple subpial transections (MSTs) superior and posterior to the lesion and over the left angular and supramarginal gyri. Six months after surgery, he began having frequent, brief episodes in which he covered both ears and described the sound of elephants or animals running. He often covered his right ear before the left (Fig. 1A). In addition, he had a frightened expression and became very quiet. The seizures worsened to include alteration of consciousness and secondary generalization and became refractory to multiple medications including carbamazepine (CBZ), lamotrigine (LTG; Lamictal), valproic acid (VPA), topiramate (TPM), phenobarbital (PB), and clobazam (CLB). Because of the frequent and medically refractory nature of the epilepsy, the child was evaluated for a second surgery at age 7 years. Ictal scalp VEEG showed an abrupt onset of low-amplitude 16- to 22-Hz beta waves associated with ear-plugging episodes, followed by a 5- to 6-Hz theta rhythm over the left temporal region, spreading to the frontal and central regions. MEG showed interictal epileptic spike sources in the left temporal, inferior, and

3 1564 D. F. CLARKE ET AL. FIG. 1. Patient 1 initially used his right hand to plug his right ear when he heard sounds of elephants running (A). Invasive video electroencephalography (VEEG) monitoring used a 109-channel subdural grid covering left frontoparietotemporal regions, inferior frontal strips, and depth electrodes to the mesial temporal structures. Ten bipolar channels were selected from the 109 subdural electrodes (B). EEG seizure of low-amplitude 50-Hz gamma activity started from electrodes 64 (posterior temporal region), 83 (superior temporal gyrus), and 94 (superior temporal gyrus, anterior to 83). The fast waves abruptly spread to electrode 71 (inferior frontal gyrus). C: Positions of IVEEG electrodes overlaid on the surgical area. Ictal-onset zone was identified in the superior temporal region at electrodes 64, 83, and 94 (solid circle), spreading to the posterior portion of the inferior and middle frontal gyri. Cortical stimulation activated the language area seen at electrodes 86, 73 (solid square), and the tongue area at electrodes 51 and 52 (solid square). The cortical excision over the left temporal lobe, including mesial temporal structures and the left frontal region, is indicated (white line). midfrontal regions. MEG auditory evoked fields showed a response in both superior temporal gyri contralateral to the monaural sound. fmri during picture naming demonstrated bilateral activation of the posterior language areas and left greater than right activation of the inferior frontal regions. Neuropsychological evaluation revealed a child who socialized well with others but who was delayed in his verbal and nonverbal abilities. IVEEG captured an abrupt onset of low-amplitude gamma ( 50 Hz) activity in the left superior temporal gyrus at the beginning of ear plugging, rapidly spreading to the midfrontal and inferior frontal head regions (Fig. 1B). Occasionally the ictal discharges spread to the left mesial temporal region with alteration of consciousness and generalized to the contralateral hemisphere with generalized tonic clonic seizures. At surgery, residual tumor was removed anterior and inferior to the previous resection. We also resected the remaining left temporal lobe, amygdala, hippocampus, and the middle to posterior region of the middle and inferior frontal gyri where epileptiform discharges remained after tumor resection (Fig. 1C). Histologic examination again showed cortical dysplasia and DNET. In the immediate postoperative period, the child had mild difficulty with expressive language, but quickly regained his presurgical language ability. Although no formal dichotic or monaural hearing tests were performed, his mother believes that he localizes well to sounds. He has been seizure free with PB and CLB for 14 months. Although he is still developmentally delayed and has occasional memory difficulties, he has been more alert and interactive with his family and peers. Patient 2 This 13-year-old ambidextrous boy had left occipital Sturge Weber syndrome, pervasive developmental disorder, and localization-related epilepsy. His development was normal before having seizures at age 18 months. His seizures consisted of eye deviation to the right, rightsided clonic activity with or without ictal vomiting, occasional secondary generalization, and a right-sided Todd s paralysis. At age 7 years, he underwent surgery to remove a left occipital lesion. Pathology results showed a leptomeningeal angiomatosis and a calcified degenerative cortex, which was consistent with Sturge Weber syndrome.

4 EAR PLUGGING IN EPILEPSY 1565 FIG. 2. Patient 2 used both hands to plug both ears when he heard unbearable roaring sounds (A). Anterior temporal lobectomy was performed because of active epileptiform discharges of spike and slow waves from the middle and inferior temporal regions and mesial temporal region. The 10-channel surface electrode was placed on the left superior temporal gyrus (B). The selected bipolar channels from the postexcisional electrocorticography captured low-amplitude ( 25 Hz) beta waves building up and lasting 25 s at electrodes 1 3, indicating a subclinical seizure on the superior temporal gyrus (C). The patient under general anesthesia with isoflurane did not have clinical seizures. Two years after surgery, he began having ictal events that consisted of bilateral ear plugging (Fig. 2A). During the events, the child described hearing an unbearable roaring sound, made a strange facial expression, cried occasionally, and verbalized bad seizure. The sound was occasionally, but not consistently, louder in his right ear. While waiting for the sound to go away, he frequently held his right ear but released the left. Subsequent to hearing the sound, he intermittently experienced eye deviation to the right and secondarily generalized tonic clonic seizures with postictal fatigue, but no Todd s paralysis. His seizures were intractable to CBZ, PB, and VPA. Ictal scalp VEEG showed low-amplitude 16-Hz beta waves over the left frontal and temporal regions associated with the ear plugging. Medium-amplitude 5- to 6-Hz spike-and-waves often followed, built up over the left frontal temporal regions, and spread to the central region, accompanied by eye deviation to the right side and generalized tonic clonic seizure. MEG showed interictal epileptic spike sources over the left superior temporal gyrus and the residual left occipital cortex, anterior and superior to the cortical excision. MEG auditory evoked field showed a response in the right superior temporal area to left monaural sound. A response was difficult to elicit to right monaural sound. fmri produced distinct language activation near the previously resected site in the left temporal region. Language activation also was found in the right temporal area. At age 12 years, he again underwent surgery. Abnormal left occipital tissue was excised. Based on the high-amplitude spike-and-slow waves from the lateral and mesial temporal regions, the anterior temporal lobe, including the mesial temporal region, also was resected (Fig. 2B). Postexcisional ECoG captured one occurrence of low-amplitude beta ( 25 Hz) waves that built up over the superior temporal gyrus and lasted 25 s (Fig. 2C). Because the EEG seizure was localized in the area of language activation on fmri, MST was performed over the superior temporal gyrus. In the immediate postoperative period, the child described the sensation that the sound is coming, but 13 months after surgery, he no longer had any of his prior spells and had no subjective hearing problems. He has been more interactive and talkative with both his family and his peers. Patient 3 This 9-year-old left-handed boy was diagnosed with linear nevus syndrome and developmental delay. He expressed language only by signs ( 100). His birth history

5 1566 D. F. CLARKE ET AL. revealed a normal pregnancy and delivery. The patient s physical examination showed linear nevi in bracelet, C- like formations along the right side of his neck and chin, and a left homonymous hemianopsia. He had no other physical findings. Neonatal seizures began at age 2 weeks, but disappeared after treatment with PB and PHT. Infantile spasms occurred at 8 months and were successfully treated with adrenocorticotropic hormone (ACTH). At months, he experienced another type of seizure characterized by motion arrest, head and eye deviation toward the left, vomiting, drooling from the left side of his mouth, and occasional head drop. Ictal scalp VEEG revealed rhythmic 2- to 3-Hz spikeand-slow waves building up over the right hemisphere with right temporal predominance, followed by flattening lowamplitude fast waves before his head turning to the left side. MRI showed a right temporal and occipital cortical dysplasia. At age 4 years, the child underwent a right anterior temporal lobectomy, an amygdalohippocampectomy, and MST over the posterior temporal and temporooccipital junction. Eight months after surgery, seizures recurred. Ictal scalp VEEG showed low-amplitude attenuated cerebral activities 1 s before he plugged his left ear. Interictal mediumamplitude sharp waves over the right posterior temporal and occipital regions disappeared during the ear-plugging episode. The EEG attenuation lasted 20 s. In addition, he displayed behavioral arrest, eye deviation to the left, and unresponsiveness. Interictal scalp VEEG showed highamplitude polyspikes or spike-and-slow waves diffusely over the right temporal, frontal, central, and parietal regions. MEG revealed interictal spike sources over the right superior temporal gyrus and the right inferior middle frontal gyri. Because of his inability to communicate verbally, he was unable to describe these experiences. The seizures were intractable to PHT, PB, VGB, gabapentin (GBP), CBZ, and TPM. His current medications are CLB and oxcarbamazepine (OXC). Because the patient had an extensive epileptic zone over the frontal, temporal, central, and parietal regions with residual posterior temporal and occipital cortical dysplasia and was unable to communicate in a languagelateralization test, he received no further surgery. DISCUSSION Primary motor findings, such as eye blinking, head version, making figure 4 signs, or posturing, may indicate a localization and lateralization of the seizure-onset zone (3,4). Complex motor manifestations that are not directly caused by a cortical discharge but are performed as a result of the seizure itself also may indicate seizure lateralization and localization. Postictal nose rubbing is a well-known motor sign, frequently seen in temporal lobe epilepsy. However, the etiology of nose rubbing, which lateralizes at seizure onset to the temporal lobe ipsilateral to the wiping hand in 90% of the cases studied, is unknown. The behavior may be a reaction to an olfactory hallucination originating from the uncus or to increased mucosal secretion and the result of impairment in the use of the contralateral limb (5). Ear plugging also is not a primary motor seizure but a motor manifestation performed in response to an auditory hallucination that is secondary to seizures involving the temporal lobe, specifically the superior temporal gyrus. Patient 3 plugged the ear contralateral to the site of seizure onset; however, he was unable to describe any specific sounds because he lacked verbal ability and had limited sign-language skill. The consistent use of his dominant left hand suggested that he showed a preference for plugging his ear with that hand. As he had no physical impairment or hearing loss on the right, we suggest that he heard, or maximally heard, the ictal phenomenon only in his left ear, contralateral to the focus of the right temporal onset seizures. Interictal MEG showed spike sources in the right superior temporal region anterior to the residual cortical dysplasia. This finding concurs with those of Wieser (2) and Penfield and Jasper (1), who described ictal onset in the primary auditory cortex as causing contralateral simple auditory hallucinations. The contralateral effect of auditory stimuli is supported by positron emission tomography (PET), fmri, and MEG studies (6,7). The other two children (patients 1 and 2), however, often covered both ears and described inconsistencies or difficulty in lateralizing the sounds they experienced. The auditory cortex receives input from both ears. Dual innervation and complex auditory processing may hinder the ability to determine the laterality of sound, as indicated by studies of dichotic listening (8). Moreover, an ictus commencing in or spreading to the secondary auditory cortex might produce identical phenomena on the side ipsilateral to seizure onset, as is believed to occur in sensory symptoms that are ipsilateral and identical to those occurring in the contralateral hemisphere (1). Alternatively, these two children may have had difficulty lateralizing their auditory auras because they were ambidextrous and had bilateral cortical areas for language. Spikes identified by MEG and co-registered with MR images (9 15) were better than scalp EEG results at localizing the ictal onset observed during IVEEG and ECoG. Furthermore, in patients with recurrent seizure disorders after craniotomy, electrical fields were unreliable for localizing seizure foci because of variations in the conductivity of the craniotomy and excisional space (16). In patient 1, the superior temporal and inferior frontal lobe seizure onset had corresponding MEG spike-source localization. In patient 2, after cortical excision of the occipital area, a seizure occurred in the superior temporal region in the area identified by MEG spike-source foci.

6 EAR PLUGGING IN EPILEPSY 1567 In patients 1 and 2, we captured EEG seizures by using subdural EEG. Subdural EEG revealed fast beta or gamma activity localized in the superior temporal region. This fast-frequency, low-amplitude activity may be characteristic of seizures involving the primary auditory cortex. Animal studies and investigative techniques in humans have found that various auditory stimuli induce gamma activity in the primary auditory cortex, although not described as ictal phenomena (17,18). Predominant fast beta or gamma activity in the EEG seizures captured during subdural grid placement (patient 1) and intraoperative ECoG (patient 2) may be a signature of this auditory hallucination seizure (19,20). In patient 1, ear plugging occurred at seizure onset before and after his first surgery, indicating an incomplete resection of the ictal-onset zone in the superior temporal gyrus where MST was performed. MEG and IVEEG demonstrated an extensive epileptic zone that was secondary to cortical dysplasia and DNET and necessitated extensive surgical excision for control of seizures. Ear-plugging seizures were identified only after initial epilepsy surgery in patients 2 and 3. The partial seizures were, however, similar to those of presurgical seizures. Two possibilities may explain the change in seizure semiology after the first surgery: an expressed neighboring focus or a developmental change in the epileptic brain. After part of the epileptic zone was removed, the neighboring focus may have expressed a new auditory aura with ear plugging that had a semiology similar to the remaining ictal symptomatic zone. Changes in ictal semiology have been reported at different ages in pediatric epilepsy (21 23). Sensory phenomena were difficult to detect or absent in infants (21). Automatisms in complex partial seizures started only in preschool-aged children (22,23). Auditory hallucinations and ear-plugging behaviors may identify the developmental auditory organization and the epileptic network in the superior temporal cortex. Our findings indicate that the ictal ear plugging may lateralize seizure onset to the contralateral temporal lobe auditory cortex of children with auditory aura. Our results also support previous reports that an auditory aura of a simple auditory hallucination implicates superior temporal lobe seizure onset. IVEEG, intraoperative ECoG, and MEG showed that epileptic spike sources and seizure onset occur in the superior temporal region in patients who display ear plugging as part of their seizure semiology. A diagnosis of seizures should be considered, especially in children with poor communication skills, if they perform consistent, repetitive, stereotyped, complex behavioral manifestations such as ear plugging. 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