Seizure activity following cochlear implantation: Is it the implant?

International Journal of Pediatric Otorhinolaryngology 76 (2012) 704–707

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Seizure activity following cochlear implantation: Is it the implant? Tulika Shinghal a,*, Sharon Cushing b,1, Karen A. Gordon c,2, Joelene F. Huber d,3, John Lee e,4, Blake Papsin f,5 a

Department of Otolaryngology, Head and Neck Surgery, University of Toronto, 2409, 1001 Bay Street, Toronto, ON M5S 3A6, Canada Department of Otolaryngology, Head and Neck Surgery, University of Toronto, Hospital for Sick Children, Room 6103C Burton Wing, Toronto, ON M5G 1X8, Canada c Department of Otolaryngology, Head and Neck Surgery, University of Toronto, Cochlear Implant Lab, Rm 6D08, Hospital for Sick Children, 555 University Ave., Toronto, ON M5G 1X8, Canada d Developmental Pediatrician, St. Michael’s Hospital, 61 Queen Street East, 2nd floor Pediatrics, Toronto, ON M5C 2T2, Canada e Department of Otolaryngology, Head and Neck Surgery, University of Toronto, St. Michael’s Hospital 30 Bond Street, 8C-118 Toronto, Ontario, M5B 1W8, Canada f Department of Otolaryngology, Head and Neck Surgery, University of Toronto, Hospital for Sick Children, 555 University Ave., Elm Wing 6103-C, Toronto, ON, M5G 1X8, Canada b

A R T I C L E I N F O

A B S T R A C T

Article history: Received 12 November 2011 Received in revised form 31 January 2012 Accepted 3 February 2012 Available online 3 March 2012

Objective: Cochlear implantation is a successful method of auditory rehabilitation. This procedure has been associated with facial nerve and vestibular end-organ stimulation suggesting potential for extracochlear stimulation. The objectives of this study were to investigate the potential relationship between cochlear implantation and seizure activity in the pediatric implant population. Methods: Local Research Ethics Board approval was obtained. The Hospital for Sick Children’s Cochlear Implant Database from 1998 to 2011 was retrospectively reviewed. Based on a multidisciplinary team, patients who received a diagnosis of seizure disorder or had been investigated for seizure-like activity were identified and reviewed. Results: Fifteen children from a group of 816 pediatric cochlear implant users were identified as having suspected seizure-like activity. Eventually 10 children were found to have seizures based on an evaluation by a pediatric neurologist and an electroencephalogram. Of these 10, only 3 children had new onset of seizures after cochlear implantation and 2 of these 3 suffered from global developmental delay and other medical comorbidities. No definite temporal connection was found between cochlear implant use and seizure activity. Conclusions: Cochlear implantation in the pediatric population continues to be a reliable and safe intervention for children. Overall the prevalence of post implantation seizure disorders in our population (0.37%) is lower than that of the overall population (0.5–1%). The presence of new-onset seizure activity following cochlear implantation is unusual and while there are theoretic possibilities of how a cochlear implant could be implicated in initiating seizures we were unable to find evidence to support this association. ß 2012 Elsevier Ireland Ltd. All rights reserved.

Keywords: Cochlear implantation Cochlear implant Seizures Epilepsy Safety Pediatric Complication

1. Introduction Cochlear implantation (CI) is an established method of auditory rehabilitation that has been successfully performed in the pediatric population for many years. This procedure has effectively benefited children with severe to profound sensorineural hearing loss (SNHL) with low rates of complication [1–5]. Complications from CI

* Corresponding author. Tel.: +1 416 946 8742. E-mail addresses: [email protected] (T. Shinghal), [email protected] (S. Cushing), [email protected] (K.A. Gordon), [email protected] (J.F. Huber), [email protected] (J. Lee), [email protected] (B. Papsin). 1 Tel.: +1 416 813 2190; fax: +1 416 813 5036. 2 Tel.: +1 416 813 6683. 3 Tel.: +1 416 867 7460x8276. 4 Tel.: +1 416 864 5306; fax: +1 416 864 5469. 5 Tel.: +1 416 813 4938; fax: +1 416 813 5036. 0165-5876/$ – see front matter ß 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2012.02.024

continue to decrease due to improvements in technology, smaller incisions, and better follow-up [6]. Nonetheless, there are several reports in the literature that address uncommon complications related to extra-cochlear stimulation. Several authors have reported facial nerve stimulation in pediatric CI users [2,7,8] and others have reported on stimulation of the vestibular end-organs via the implant array [9]. Given these 2 well documented targets of aberrant current, we asked whether or not different avenues of current spread could lead to other neurologic side effects, and in particular seizures. A seizure is an episode of abnormally synchronized and high frequency firing of neurons, primarily in the cerebral cortex, which results in abnormal behaviors; abnormal body movements, sensations or changes in tone; and/or changes in level of alertness by the individual. An individual is considered to have epilepsy when unprovoked seizures recur over a period of time without obvious precipitants. Seizures can be partial seizures (the underlying pathophysiology or anatomy has a focal origin, and are simple

T. Shinghal et al. / International Journal of Pediatric Otorhinolaryngology 76 (2012) 704–707

partial if consciousness is not altered and complex partial if consciousness is altered); or generalized seizures (widespread involvement of the brain and causing impaired consciousness); or may be partial seizures with secondary generalization (may begin as a partial seizure but extend to bilateral cerebral hemispheric involvement) [25]. Activation of specific cortical regions by sensory stimuli or of less restricted areas of the brain by cognitive stimuli is known to induce apparently generalized seizures in predisposed patients [10]. There are a variety of conditions that have a high likelihood of resulting in a chronic seizure disorder such as severe head trauma, strokes, infections and abnormalities in CNS development [11,12]. Our question about a potential association between CI and seizures was prompted by the presentation of a child who developed new onset seizures following CI. We found no previous reports of such cases in the literature but hypothesized that CI might contribute to a communication between the implant and the central nervous system. Seizure disorders have been associated with other forms of otologic and neuro-otologic surgery. Reports of epilepsy following middle-fossa approaches for both vestibular schwannoma and temporal encephaloceles have been documented with extradural retraction. In this report, generalized tonic–clonic seizures developed three days and 4 weeks post-operatively [13]. It is postulated that during middle-fossa surgery the temporal lobe may be more susceptible to epilepsy if there is direct trauma to the brain or if retraction induces ischemia or hemorrhage. In addition, Migirov et al. described a mastoidectomy procedure on a 16-yearold boy who suffered from a cholesteatoma. The patient presented 5 days later with seizures and a subdural empyema [14]. These cases demonstrate that post-surgical irritation of the temporal lobe, either from prolonged retraction or infection, can potentially lead to new-onset seizures. This could include the theoretic risk of temporal lobe dural exposure at the level of the tegmen following standard mastoidectomy in addition to dural exposure in the well created for the receiver stimulator in CI surgical patients. These potential risks, in addition to the redundancy of the implant electrode that is curled in the mastoid cavity and the distant ground placed under the temporalis muscle, might lead to inadvertent stimulation of the temporal lobe putting the child at risk for seizure. To date, no published report has described an association between CI and seizure activity. The purpose of this article was to investigate the overall incidence of seizure disorder in our CI population and to determine whether a particular relationship exists between seizure and CI in the pediatric population. 2. Methods Research ethics board approval was obtained. The Hospital for Sick Children’s Pediatric Cochlear Implant Database from 1998 to 2011 was retrospectively reviewed. Based on a multidisciplinary team, patients who carried a diagnosis of seizure disorder or had been investigated for a question of seizures were identified. These patients’ charts were reviewed for socio-demographic information and past medical history with special attention to neurological conditions, including any history of seizures, onset of seizures, the temporal relationship between CI use and seizures, neurological investigations as well as management of the seizure disorder. 3. Results We reviewed the medical histories of 816 children who underwent CI from 1998 to 2011. In this group, 15 children were identified as having suspected unprovoked seizures (Table 1). There were 10 boys and 5 girls. The average age at CI was 2.6 years.

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Amongst the 15 identified cases, there were abnormal movements and posturing in 14 children and abnormal staring in 1 child. All patients underwent an assessment by a pediatric neurologist. Five children were eventually found to have no evidence of seizures or epilepsy. Seven other children were diagnosed with a seizure disorder. All 7 had onset of seizures prior to CI placement. None of the children in this group showed changes in the characteristics of their seizures or in their management following CI. Three children were identified as having new-onset of seizures following CI. One of these 3 children suffered from Waardenburg’s syndrome (type 4) with Hirshsprung’s disease, profound SNHL and developmental delay. He received a unilateral CI Nucleus 24CA placed on the right side at the age of 20 months in 2004. There were no complications during the surgery. At 23 months of age, this child had an episode of generalized tonic–clonic seizures. Genetic and neurologic assessment found no underlying condition, which could explain the onset of seizures. An electroencephalogram (EEG) failed to demonstrate evidence of epileptiform activity. The child was treated nonetheless given the clinical history with phenobarbital. He did well for a period of 1 year and was subsequently weaned from the phenobarbital. He developed a recurrence of seizures 5 months later and phenobarbital was reintroduced. There was no apparent temporal relationship between the onset of seizures and CI use. His seizures became difficult to manage and he underwent numerous trials of antiepileptics without success. An EEG performed in 2007 demonstrated significant generalized epileptiform activity. Fortunately, since 2008, his epilepsy has been relatively well controlled on zonisamide. The second in this group was an otherwise healthy child who at the age of 3 years received a CI (Nucleus 24M) on his right side. His surgery went well and there were no complications. He used his CI successfully for numerous years after CI. At 9 years, of age the patient suffered from 3 episodes of generalized tonic–clonic seizures. He was investigated by a pediatric neurologist and was found to have an abnormal EEG with focal centrotemporal epileptiform spike and wave discharges from the left hemisphere. The seizures seemed to be associated with sleep deprivation and occurred primarily when the patient was fatigued. There was no clear connection between the use of CI and the seizure activity. The remaining child in the group of 3 children with seizures presenting after CI had a neurodevelopmental diagnosis of Klinefelter’s syndrome, cleft palate, SNHL, cortical blindness and global developmental delay [15]. The child received a unilateral CI (Nucleus 24M) on the right side at the age of 17 months. The patient was admitted to the hospital at 2 years of age for meningitis. At 7 years of age, he was investigated by pediatric neurology due to episodes of tonic posturing with his arms. He had a video EEG performed which showed one electroclinical seizure consistent with bilateral arm tonic posturing. A few months later, concerns were relayed by the caregivers about a possible association with CI use. In this case, an implant evoked EEG was performed and found to be abnormal with one electroclinical brief tonic seizure probably precipitated by the first external cochlear device placement with 08 sensitivity. This finding was however inconsistent and non-reproducible with further events. The patient appeared to have a low threshold for startle responses induced by sound, but no epileptiform changes were documented on EEG. The patient had another EEG performed in 2010 due to ongoing startle responses and tonic posturing of arms. The video EEG captured many episodes of posturing but none associated with clear ictal EEG changes. An EEG done in 2011 with the CI switched off showed clinical events of myoclonic jerks and one associated with left central temporal wave discharge with slow background for age. These investigations found no evidence for a relationship between

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Table 1 Patient characteristics, comorbidities, seizure onset and investigations. Patient

Age (years)

Age at CI (years)

Sex

Seizure activity

Seizure onset

Epilepsy

EEG

Comorbidities Premature, cerebral palsy, visually impaired, development delay Intraventricular hemorrhage, hydrocephalus with ventriculoperitoneal shunt Post meningitis (cortical blindness, cerebral palsy, developmental delay, seizure disorder) Post meningitis (seizure disorder) Premature, cerebral palsy, right hemiplegia, retinopathy, hydrocephalus, intraventricular hemorrhage, ventriculoperitoneal shunt, seizure disorder Developmental delay, atretic cephalocele Premature, twin–twin transfusion syndrome, right transverse sinus thrombosis Healthy Healthy Hirschsprung’s, Waardenburg’s, developmental delay

1

8

2

Male

No

N/A

No

No

2

11

3

Female

No

N/A

No

No

3

7

2

Male

Yes

Before

Yes

Yes

4 5

14 9

1 2

Female Female

Yes Yes

Before Before

No No

Yes Yes

6

11

4

Male

Yes

Before

No

Yes

7

7

1

Male

Yes

Before

No

Yes

8 9 10

17 15 8

5 9 1

Male Male Male

No No Yes

N/A N/A After

No No Yes

11 12

14 12

3 1

Female Male

No Yes

N/A After

No Yes

13

15

3

Male

Yes

After

Yes

14 15

11 8

2 0

Female Male

Yes Yes

Before Before

Yes Yes

No No Yes (significant generalized epileptiform activity) Yes Yes (clinical events of myoclonic jerks and one associated with left central temporal wave discharge with slow background for age) Yes (focal centrotemporal epileptiform spike and wave discharges from the left hemisphere) Yes Yes

the seizures and CI use. This child is currently being treated with lamotrigine. 4. Discussion Sensorineural hearing loss and seizure disorders share a number of common risk factors including for example, prematurity and meningitis. A number of reports exist in the literature outlining the safety of CI in the setting of an established seizure disorder in both adults and children [16,17]. Successful CI has been performed even in the setting of disorders such as schizencephaly, a developmental disorder, which manifests with motor dysfunction, optic nerve hypoplasia, microcephaly, general developmental delay, hemi/quadriparesis and epilepsy. In general, seizure disorders are not considered to be a contraindication to CI. Overall, we found that 1.8% of our CI population was suspected to have seizure-like activity and eventually only 0.37% developed new-onset seizures after implantation. In comparison, the overall annual incidence of unprovoked seizures and epilepsy is 55/ 100,000 and 30/100,000, respectively [18]. Epilepsy affects approximately 0.5–1% of all children through the age of 16 years [19,20]. The median age of seizure onset is between 5 and 6 years. The risk of epilepsy appears to be the highest in patients with an associated serious neurologic abnormality, such as developmental delay or cerebral palsy [19]. To our knowledge, seizures have previously not been reported in the literature as an adverse effect of CI. However, there are several possible contributing factors that could be implicated in the development of seizures following CI. Theoretically there are 2

Healthy Klinefelter’s syndrome, cleft palate, cortical blindness, global developmental delay

Healthy

Pendred syndrome Meningitis with extensive bilateral cerebellar frontoparietal infacts

general mechanisms by which CI could trigger seizures due to either (1) mechanical/surgical irritation of the cortex or (2) to extra-cochlear electrical stimulation. Specifically, acute seizures in the immediate post-operative period would raise suspicion of intracranial or epidural bleeding. A case of intracranial bleed postimplantation in an 80-year-old male has been reported. On postoperative day four, he developed incontinence, slurred speech and became weak. This was felt to arise from trauma to the diploic veins during surgery [21]. Another report discusses a 13-monthold boy who developed contralateral sixth nerve palsy 12 h after CI. He was found to have a large right temporo-parietal acute extradural hematoma adjacent to the internal receiver of the CI. The child had dural exposure during surgery and it was thought that trauma to the posterior parietal branch of the middle meningeal artery could be implicated [22]. Thus, it is possible that the placement of implants causes small epidural bleeds, particularly in children where dural exposure is common during tie-down of the device’s receiver stimulator. Emissary veins may be opened by the drill passages used to anchor the sutures for the receiver/stimulator. Certainly irritation of the temporal lobe could occur at the drilled receiver stimulator bed even in the absence of bleeding. There is an additional risk of temporal lobe dural exposure during mastoidectomy at the level of the tegmen. Finally, the electrical field generated by the electrodes may have nonacoustic side effects on the cortex. In our group of 816 children using CI, we identified only 3 (0.36%) who developed seizures following CI. However, two of these three children suffered from severe developmental delay and confounding medical comorbidities. One child suffered from

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Waardenburg’s syndrome which is known have an association with seizures [23]. Another child suffered from Klinefelter’s syndrome which is also associated with seizures [15]. In addition to Klinefelter’s syndrome, this child also suffered from meningitis before the onset of seizures. The remaining third child was healthy and had successfully used his CI for 8 years before developing seizures. Apart from the new onset of the seizures after CI, no additional features of the seizure disorders supported an association with CI. We believe that in order to clarify any possible association between CI use and seizures it is important to identify the temporal association. However, this is difficult given that seizure activity may be infrequent. As opposed to the incidence of seizures, CI use is frequent and sometimes patients wear their devices even when they sleep. Therefore, in order to elucidate a clear relationship between these two factors, it may be necessary that patients avoid using their CI periodically. 5. Conclusion Cochlear implantation in the pediatric population continues to be a reliable and safe intervention for children with severe to profound SNHL. It has transformed developmental outcomes and provided access to spoken language [24]. Overall the incidence of seizure disorders is lower than that in the overall population. The presence of new-onset seizure activity following CI is rare and, while there are theoretic possibilities of how a CI could be implicated in initiating seizures, we have not found evidence to support this association. Careful evaluation of any child who develops seizures either in an immediate or delayed fashion following CI is imperative. Implant triggered EEG can be a useful tool in determining if there is any correlation between seizure activity and implant activation. References [1] J. McJunkin, A. Jeyakumar, Complications in pediatric cochlear implants, Am. J. Otolaryngol. 31 (March–April (2)) (2010) 110–113. [2] H.G. Kempf, K. Johann, T. Lenarz, Complications in pediatric cochlear implant surgery, Eur. Arch. Otorhinolaryngol. 256 (3) (1999) 128–132. [3] T. Davids, J.D. Ramsden, K.A. Gordon, A.L. James, B.C. Papsin, Soft tissue complications after small incision pediatric cochlear implantation, Laryngoscope 119 (May (5)) (2009) 980–983.

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