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Electroencephalography of Seizure-Like Movements During General Anesthesia with Propofol

Seizures or Nonepileptic Events?

Li, Yi MD; Flood, Pamela MD, MA; Cornes, Susannah MD

doi: 10.1213/XAA.0000000000000212
Case Reports: Clinical Care
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Seizure-like behavior is an uncommon yet worrisome phenomenon during anesthesia with propofol. The current case report describes a 23-year-old man admitted for elective surgery who experienced several seizure-like episodes after induction with propofol and during a desflurane-based general anesthetic that were so severe it was not possible to complete the procedure. A second surgery was rescheduled 2 days later with simultaneous scalp electroencephalographic (EEG) recording and general anesthesia with propofol and fentanyl. During the second operation, he again experienced numerous episodes of generalized shaking movements. Simultaneous intraoperative EEG recording showed a background of diffuse beta and alpha frequencies interspersed with periods of pseudoperiodic delta activity; electrographic seizures were not apparent. With this information, muscle relaxants were given and the procedure was performed without difficulty. This is the first report of apparent seizure-like activity during anesthesia with propofol of an otherwise relatively healthy adult, in which concurrent EEG recording demonstrates the nonepileptic nature. The current case demonstrates that, at least in some instances, these concerning movements are not seizure related. Concurrent EEG monitoring may be helpful to evaluate the nature of the episodes in select cases.

From the *Department of Neurology, University of California, San Francisco, California; Department of Neurology, Xiangya Hospital, Central South University, Changsha, China; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford Hospital and Clinics, Palo Alto, California; and §Department of Neurology, UCSF Comprehensive Epilepsy Center, San Francisco, California.

Accepted for publication April 16, 2015.

Funding: YL is supported by funding from the National Natural Science Foundation of China (81100967) and Specialized Research Fund for the Doctoral Program of Higher Education (20110162120002).

The authors declare no conflicts of interest.

Address correspondence to Pamela Flood, MD, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford Hospital and Clinics, 300 Pasteur Ave., Palo Alto, CA 94140. Address e-mail to pflood@stanford.edu.

Propofol has been used for induction and maintenance of general anesthesia since approval by the Food and Drug Administration in 1989, and it has also been widely chosen as a treatment for refractory status epilepticus.1 Its potent anticonvulsive properties have been well demonstrated, and it is favored by clinicians because its short half-life facilitates fast titration and shorter recovery time to enable rapid clinical assessment. Despite its use to treat seizures in some cases, a few propofol-related seizure-like episodes have been reported previously in adult patients undergoing surgery. Although a small percentage of cases have included baseline electroencephalography (EEG) analysis after the episode, there is understandably a paucity of EEG data obtained during actual events. As a result, abnormal movements are often assumed to be seizure in the absence of data to the contrary.2,3

We present the first report of apparent seizure-like activity during general anesthesia with propofol in which concurrent EEG recordings demonstrate an absence of seizure activity. EEG was obtained in this case because of previous similar seizure-like movements during anesthesia with desflurane after induction with propofol. The repeated occurrence of abnormal movements, presented here, while the patient received propofol suggests that some individuals may be prone to developing this phenomenon. We suggest that intraoperative EEG could be considered to diagnose and characterize these seizure-like events and to avoid an incorrect diagnosis of seizure or epilepsy. The patient agreed to publication of this case report.

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CASE REPORT

A 23-year-old man with a history of stable HLA-B27 seronegative spondyloarthropathy and inflammatory bowel disorder, diagnosed in December 2012, was admitted for elective surgical repair of a recurrent pilonidal cyst in July 2013. He underwent general anesthesia induced with propofol and maintained with desflurane. During the surgery, he was noted to have 30 seconds of generalized shaking and was treated with a 100-mg propofol bolus followed by a 100 μg/kg/min infusion. Desflurane was discontinued. A second period of generalized shaking occurred 3 minutes later and again several minutes thereafter, at which point propofol was increased to 200 μg/kg/min. Surgery was terminated, and he was taken out of the operating room for head computed tomography, which was unremarkable. Dilantin was administered, and propofol was soon tapered off.

Overnight, his trachea was easily extubated and he was noted to be awake, alert, able to follow commands, and without further seizure-like activity. An EEG was obtained the next day and was essentially normal (Fig. 1). Magnetic resonance imaging was performed and was unremarkable. No other clear precipitant for seizure was identified. There were normal metabolic laboratories, no evidence of infection or fever, history of febrile seizures, prior head injury, or concern for meningitis. Medications had included sulfasalazine and methotrexate over the past several months, and there had been no medication changes, history of heavy alcohol use, or recreational drug use.

Figure 1

Figure 1

A second surgery for the completion of pilonidal cyst removal was rescheduled 2 days later. Given the prior events concerning for seizure, the patient had scalp EEG recording during the operation. Propofol and fentanyl were used because of the relatively few reports of seizure-like movements with propofol alone and its prior efficacy in stopping the movements. The patient again experienced numerous episodes of severe, generalized shaking movements beginning approximately 35 minutes after induction and occurring 6 times over the next 2 hours. With confirmation of the absence of epileptiform activity, a nondepolarizing muscle relaxant was given and the surgery was completed.

Figure 2

Figure 2

The intraoperative scalp EEG recording before surgery showed a normal mixture of alpha and beta frequencies with a posterior dominant rhythm of 10 Hz. An increase in beta frequency activity was observed during induction followed by high-amplitude polymorphic delta slowing that persisted for 10 minutes. Thereafter, the recording consisted of diffuse beta and alpha frequencies interspersed with periods of pseudoperiodic delta activity. Movement artifact was noted during the episodes of apparent seizure-like activity. However, no epileptiform activity or electrographic seizure activity was recorded during the spells (Fig. 2). Antiepileptic medications were therefore not escalated. The patient again recovered and his trachea was easily extubated. He remained seizure-free.

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DISCUSSION

The patient in the present report experienced what appeared to be seizure-like activity several times over 2 separate surgeries conducted with propofol alone or used in conjunction with desflurane. In the second surgery, concurrent EEG confirmed the absence of electrographic seizure. These seizure-like events were therefore nonepileptic, possibly representing myoclonic activity originating from subcortical or spinal regions. Although the patient was generally healthy, he may have had hyperactive reflexes because of his history of spondyloarthropathy, resulting in a predisposition to develop myoclonic activity resembling seizures.

The semiology of seizure-like activity induced by propofol was originally categorized into 5 groups by Walder et al.2: generalized tonic-clonic (GTC), focal motor seizures, twitching and rhythmic movements not preserved as GTC, opisthotonos, and involuntary movements. GTC and motor seizures were described to be slightly more common and also most worrisome because of a possible epileptic origin. Seizure-like movements have been described in both surgical patients with epilepsy4 and in those without a history of seizure or established risk factors for epilepsy. The electrophysiologic characteristics of the phenomena have not been described because generally the rare appearance of seizure-like movements is not anticipated and EEG cannot be completed.

There has been a single case described in the pediatric literature of an infant with choreiform and jerking movement during the recovery from propofol anesthesia, at which time EEG demonstrated “blocking alpha-waves associated with symmetrical delta-theta waves (voltage 50–100 μV).”5 It has been theorized that this slow wave pattern may be related to the hyperpolarizing influence of propofol affecting the normal balance of afferent input to thalamus from the cortex and reciprocal thalamocortical projections, creating a bistable oscillation of cortical neurons at a frequency as low as 1 Hz.6 This slow oscillation pattern is thought to generate the slow wave scalp EEG correlate seen with propofol.

Propofol has been explored controversially for both anticonvulsive and proconvulsive effects. It facilitates the activation of γ-aminobutyric acid receptors similar to benzodiazepines although through a different mechanism. In addition, it interferes with calcium influx and blocks hippocampal sodium channels,7 which may contribute to its anesthetic and anticonvulsive properties. However, propofol has been found to be associated with central nervous system excitation via glycine antagonism occurring in subcortical structures.8 Studies also suggest that propofol-induced paradoxical excitation may result from an interaction between γ-aminobutyric acid type A receptor and intrinsic membrane slow potassium current, which enables a switch from baseline interneuron synchrony to propofol-induced interneuron antisynchrony.9 Various studies have been done to explore the dynamic neuronal alterations associated with propofol, including magnetoencephalography, electrocorticography, and EEG in human and animal models. However, there remains no clear model mechanism as to how propofol predisposed to seizure-like movements.

Some authors have explored the possibility that the risk of abnormal movements with propofol is related to loading doses6 or the rate of change in propofol concentration.2,3 The current case, however, illustrates the potential to have abnormal movements at varied concentrations (Fig. 3). It also raises the question as to whether some individuals are more prone to abnormal movements during anesthesia with propofol, given the repeated occurrence during 2 separate procedures.

Figure 3

Figure 3

The relative proconvulsant properties of anesthetic medications have been previously explored, although there is a paucity of EEG characterization of ictal events. Sevoflurane induced seizure-like movements in an otherwise healthy volunteer without epileptogenic EEG activity. However, in this case, ongoing recording demonstrated sharp and slow waves accompanying clinical seizure at higher sevoflurane concentrations that was aborted by giving propofol.10 Convulsant properties of sevoflurane and propofol have been directly compared in healthy adults. Epileptiform discharges were identified in all subjects anesthetized with sevoflurane at 2 minimal alveolar concentrations with 3 subjects having seizure activity. No epileptiform activity was seen in the 8 subjects anesthetized with propofol.11 Similarly, it has been argued in the electroconvulsive therapy literature that anesthetics including ketamine and etomidate enable higher quality seizures to be induced than propofol,12 implicating propofol as relatively less epileptogenic.

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CONCLUSIONS

In summary, we present a case in which propofol was associated with seizure-like movements that were demonstrated by EEG to be nonepileptic in nature. In this case, the individual recovered easily from surgery without the need for antiepileptic treatment. We submit that some individuals may be more prone to abnormal movements during general anesthesia. When there is a history of abnormal movements during anesthesia, intraoperative EEG may allow exclusion of seizure activity, thus avoiding unnecessary treatments. In the absence of concurrent EEG, the practitioner cannot be certain whether seizure-like movements during anesthesia are actual seizures.

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