Management of post-operative delirium following stereoelectroencephalography electrode placement for drug resistant epilepsy: Lessons learned from two case reports.

Post-operative delirium (POD) represents a unique challenge in the care of any surgical patient but is especially challenging in neurosurgical inpatient management due to a host of potentially significant predisposing factors. Patients undergoing stereoencephalography (SEEG) for diagnosis of drug resistant epilepsy are at unique risk due to safety concerns, yet POD has been underdiscussed in this population. Patients should be counseled pre-operatively about their risk and subsequent steps be taken post-operatively. We present two cases of POD status-post SEEG and propose a mechanism by which future post-operative care be coordinated by the physician, patient, and patient's family.

Introduction

Post-operative delirium (POD) is an acute, fluctuating disruption in attention and cognition that is associated with altered perception, inappropriate behavior, changes in awareness, and disorganized thinking [1], [2], [3]. Often expression of POD cannot be explained by a pre-existing disorder and can impair ability to comply with medical care [4], [5]. Diagnosis and treatment are complicated by a multitude of interactions between pre-operative vulnerabilities with intra-operative and post-operative precipitating factors [6], [7].

Patients undergoing neurosurgical interventions are at unique risk for POD [4]. They require frequent neurologic checks, have baseline deficits with neurologic and metabolic derangements, and neurosurgical related brain injury [2], [5], [8]. In this population factors such as age, functional and neurologic impairment, and structural comorbidities of the brain (epilepsy, ischemia, etc.) have all been shown to be predisposing factors to delirium [3], [9].

Patients undergoing neural implantation are particularly vulnerable to POD. Research investigating POD in Parkinson’s patients with deep brain stimulation (DBS) electrodes suggest that there is a direct psychotropic effect of surgical implantation of electrodes that contributes to POD [10]. Yet, there has been little research in patients undergoing stereoelectroencephalography (SEEG) surgery, where depth electrodes are implanted directly into the brain for localization of epileptic foci. Hyperactive delirium is of particular interest in this population because of the potential for self-harm.

Although there is substantial risk, by aborting the SEEG procedure before epileptic foci localization, patients cannot undergo a subsequent surgical procedure aimed at seizure control, typically their last remaining option. Thus, pre-operative risk mitigation and discussing the potential for POD can allow therapeutic alignment between patient, family and treatment team about delirium management. This paper reviews two cases of POD in patients undergoing SEEG neuromonitoring and proposes how to mitigate complications post-operatively if a patient becomes acutely delirious.

Case reports

Case 1

A 20-year-old female patient presented to the University of Colorado Neurology Department in 2015 with a 4-year history of drug resistant focal epilepsy. She subsequently underwent three phase 1 video-EEG (VEEG) sessions in the epilepsy monitoring unit (EMU) over a seven-month span. During the first session, the patient had an altercation with her parents and asked for security to escort them from her room. She then was adamant about leaving herself. She had completed the VEEG session but her final magnetic resonance imaging (MRI) had to be completed as an outpatient. Two subsequent phase 1 evaluations were without further altercations. VEEG helped localize seizure onset to the right posterior temporal lobe along with MRI findings of heterotopic gray matter along the right hippocampus and medial right temporal lobe.

In 2019 the patient presented to the University of Colorado Neurology Department for surgical consideration. A multi-disciplinary team recommended phase 2 invasive neuromonitoring using SEEG to further localize seizure onset. Psychiatric evaluation was performed prior to surgery and the patient was deemed an appropriate surgical candidate. Electrodes were implanted in the temporal occipital pole, anterior temporal pole, amygdala, anterior, middle and posterior hippocampus, posterior periventricular nodular heterotopia, temporal occipital junction and insula.

On post-operative day 1, the patient demonstrated severe agitation. She attempted to remove her electrodes and slam her head against the bed aiming at the surgical site. The patient was physically restrained by multiple individuals and given 5 mg Haldol and 4 mg Ativan to sedate and calm her.

An emergent consultation with psychiatry deemed the patient lacked decision making capacity and was a potential active harm to herself and staff. The treatment teams deemed it prudent to remove electrodes over safety concerns. The family and patient showed unwillingness to consent for explantation surgery. Ultimately consent was obtained, though family expressed a strong preference the electrodes remain. Legal counsel advised the neurosurgical team to not remove the electrodes unless necessary. Thus, the patient and family were advised that the next incident of any agitation/antagonism would result in immediate removal.

The patient was left in the intensive care unit (ICU) for better control of environment. She was given a sitter for monitoring and safety. She had successful capture of seizures and was explanted uneventfully on hospital day 23 without further incident.

Case 2

A 34-year-old male presented to the University of Colorado Neurology Department in 2018 with a 12-year history of drug resistant focal epilepsy. He was scheduled for a phase 1 EMU study which was rescheduled on the day of admission as the patient believed he was only having a half day test opposed to a multi-day study. His reasoning for rescheduling was that he was “not in the right mental space to tolerate the test”. He was later admitted for his phase 1 evaluation in the EMU using VEEG and completed the study with no disturbances. The pre-surgical hypothesis was left temporal lobe, non-lesional epilepsy with no obvious anatomical abnormalities on MRI.

In 2019 a multi-disciplinary team recommended SEEG to further localize seizures for potential surgical intervention. Prior to surgery the patient was evaluated by psychiatry and deemed an appropriate surgical candidate.

While under observation in the EMU after electrode implantation, the patient had multiple episodes of agitation suspected to be secondary to nicotine and marijuana withdrawal and expressed interest in leaving against medical advice (AMA). During these episodes he threatened to pull out his electrodes. He was counseled on the adverse and potentially life-threatening outcome of electrode tampering and subsequent ineligibility for future epilepsy surgery. Psychiatry noted that during periods of agitation the patient lacked capacity to understand the consequences of leaving the hospital with electrodes in place. He was given 2 mg Ativan once and put on Quetiapine 25 mg on post-operative day 1 in response. The patient went on to have multiple target seizures and was successfully explanted on hospital day four.

Following explantation, the patient was still severely agitated and expressed interest in leaving the hospital. He was counseled on the post-operative risks and informed that leaving AMA would prevent future surgical interventions due to concern over treatment compliance. The patient was able to calm down, though had repeated cycles of agitation where he threatened to leave until discharged 24 h later.

Discussion

Well known risk factors for POD include increased age, cognitive impairment, substance abuse, and many others [11], [9]. These vulnerabilities interact with intra-, peri-, and post-operative factors to result in an acutely delirious state [12], [13], [5]. In particular, it has been proposed that there is a direct psychotropic effect of intracranial electrodes that contributes to POD [10]. Thus, patients following SEEG placement are a particularly vulnerable population, but no guidance exists on POD in this population.

Pre-operative substance use is a modifiable risk factor for POD. In our two case reports, both patients had significant substance use with abstinence contributing to agitation while hospitalized. Additionally, both of these patients had documented issues tolerating previous phase 1 studies and difficulty abstaining from substances for recommended periods of time (e.g. prior to WADA testing). More thorough documentation of these occurrences may enlighten the care team to the possibility of such situations during phase 2 studies. We propose detailed documentation regarding prior studies, duration of substance abstinence prior to hospitalization and patient tolerance of the prior monitoring to be part of the discussion at epilepsy surgery patient care conferences.

As well, patients and families need to be informed of the potential of POD and the risk it poses to a patient before electrode placement. Identification of surrogate decision makers and assent for electrode removal if needed for safety concerns can be obtained pre-operatively. Thus, patients and families are able to make better informed decisions and allows for alignment of the patient, family and treatment team on the surgical treatment plan.

Post-operatively, if a patient develops POD re-orientation and modification of risk factors is necessary. As well, decision making capacity should be evaluated using standard hospital protocol. If the patient lacks decision making capacity then the pre-determined medical durable power of attorney (MDPOA) should be reached for treatment discussion. If the MDPOA is not available or no one is designated, legal should be involved, particularly if there is a disagreement about explantation over safety concerns between the treatment team and patient/family. Escalation to this point is hoped to be avoided by the pre-emptive conversations and decrease in substance use before surgery.

As demonstrated in these case reports, patients that have hyperactive delirium after SEEG can pose unique risk of harm to themselves. By having an external conduit via the electrodes, pulling at the electrodes and aggressive movement of the head can result in neurologic damage that can have devastating consequences. Thus, we propose several steps that can mitigate the risk of POD and lessen the decision making burden post-operatively in the event the patient becomes delirious.

Conclusion

Patients undergoing SEEG neuromonitoring for drug resistant epilepsy are at particular risk of POD and have unique safety concerns. Yet, there is a paucity of literature about POD in patients undergoing SEEG monitoring. Thus, we propose several steps pre-operatively that can help reduce the risk of POD and ways post-operatively that POD can be mitigated and addressed by the treatment team.

Funding

No funding was received for this research

Declarations of interest

None.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study formal consent is not required.

Contributions

All authors contributed to the article’s conception and design. Material preparation, data collection, and analysis were performed by K. Belanger, F. Grassia and S. DeStefano. The first draft of the manuscript was written by K. Belanger and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.