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\begin{document}

\title{Presumed first episode of non-convulsive status epilepticus as the cause
of postoperative disorder of consciousness following the completion of
general anesthesia: A case report}



\author[1]{Yumi Tsuzuki}%
\author[2]{Yusuke Ishida}%
\author[1]{Mikiko Tomino}%
\affil[1]{Tokyo Medical University Hospital}%
\affil[2]{Tokyo Medical University}%


\vspace{-1em}



  
  \date{May 28, 2024}


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\textbf{Presumed first episode of non-convulsive status epilepticus as
the cause of postoperative disorder of consciousness following the
completion of general anesthesia: A case report}

\textbf{Authors}

Yumi Tsuzuki, Yusuke Ishida, Mikiko Tomino

Department of Anesthesiology, Tokyo Medical University, 6-7-1
Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan

\textbf{Corresponding author}

Yusuke Ishida

Department of Anesthesiology

Tokyo Medical University

6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan

Tel.: +81-03-3342-6111; Fax: +81-03-5381-6650

Email: yishida14anes@gmail.com



\textbf{Abstract}

Disorder of consciousness (DOC) has various etiologies. Here, we report
a case in which DOC following general anesthesia was suspected as being
due to the first episode of non-convulsive status epilepticus (NCSE). An
elderly man in his 80s underwent uneventful tumor resection surgery
under general anesthesia for extramammary Paget's disease. After the
procedure, he regained consciousness following anesthesia
discontinuation, and was extubated. Soon after extubation, however,
although his respiratory status remained stable, his level of
consciousness deteriorated to a Glasgow Coma Scale (GCS) score of
E1V1M1. Head computed tomography and magnetic resonance imaging scans
indicated no abnormal findings. Subsequently, involuntary movements were
noted in his left upper limb. Suspecting an epilepsy episode, diazepam
was administered, leading to an improvement in the level of
consciousness (GCS: E4V5M6). Based on the improvement in consciousness
after diazepam administration, we strongly suspected NCSE.

\textbf{Keywords:} Disorder of consciousness (DOC), electroencephalogram
(EEG), non-convulsive status epilepticus (NCSE), general anesthesia



\textbf{Background}

Disorder of consciousness (DOC) is a state of prolonged altered
consciousness, which can be categorized into coma, vegetative state, or
minimally conscious state based on neurobehavioral function {[}1{]}. The
causes of DOC are diverse and can include cerebrovascular disorders,
cardiac conditions, drug intoxication, hypoglycemia, infections, as well
as psychiatric abnormalities {[}2{]}. DOC can lead to irreversible
sequelae if early intervention is not provided. Therefore, early
diagnosis and treatment are of paramount importance {[}3{]}. Indeed,
diagnosing DOC during the perioperative period can be challenging due to
the effects of anesthesia. We encountered a patient who developed
impaired consciousness after surgery, following awakening and
extubation. Based on his clinical presentation, a first episode of
non-convulsive status epilepticus (NCSE) was considered as the cause of
his DOC. Here, we provide a report of this case along with a literature
review to support our findings and contribute to the existing knowledge
on this topic. The patient's written, informed consent was obtained for
publication of this case report.

\textbf{Case presentation}

The patient was an elderly man in his 80s, 148 cm tall, weighing 50.0
kg, who presented to a nearby clinic with discomfort in the inguinal
region. Further investigation led to a diagnosis of extramammary Paget's
disease, for which surgical excision under general anesthesia was
planned. The patient had a medical history of hypertension and
asymptomatic cerebral infarction and was on aspirin. He had no
significant family history. Electrocardiography revealed complete right
bundle branch block, and blood tests did not show any notable
abnormalities.

Anesthesia induction was performed with propofol 60 mg, fentanyl 100 \selectlanguage{greek}µ\selectlanguage{english}g,
remifentanil 0.1 \selectlanguage{greek}µ\selectlanguage{english}g/kg/min, and rocuronium 50 mg. Maintenance of
anesthesia was achieved using sevoflurane 1\%, remifentanil at a rate of
0.1-0.15 \selectlanguage{greek}µ\selectlanguage{english}g/kg/min, and intermittent administration of rocuronium 10 mg.
An 8 mm endotracheal tube was used for intubation. Intraoperatively, the
patient's hemodynamics and oxygenation were stable without any
significant abnormalities. Brain function monitoring to assess sedation
levels was not performed intraoperatively, was not used to assess
sedation levels. The surgery lasted for 2 hours and 49 minutes. The
surgical procedure was completed uneventfully, following which
administration of anesthesia was discontinued. When the end-tidal
concentration of sevoflurane reached 0.1-0.2\%, the patient was
awakened, and eye opening was observed. After confirming the patient's
consciousness, sugammadex was administered, and extubation was
performed. A few minutes after extubation, the patient's level of
consciousness was observed to decrease, subsequently reaching a Glasgow
Coma Scale (GCS) score of E1V1M1. His respiratory status remained
stable. Considering the possibility of the effect of residual opioids,
naloxone was administered, but with no change in the level of
consciousness. His body temperature was 37.0 . Prompt blood gas
analysis was performed, which revealed normal pH and electrolyte levels.
There were no signs of hypoglycemia (blood sugar 110mg/dL), and no
specific findings to explain the decrease in consciousness level.
However, due to the emergence of right conjugate eye deviation, further
investigations were conducted to evaluate for an intracranial pathology.
Both head computed tomography and magnetic resonance imaging scans were
performed, but no abnormal findings, such as new brain infarctions or
intracranial hemorrhage, were detected (Figures 1 and 2). Since there
were no respiratory or circulatory abnormalities, re-intubation was not
performed. Preoperative systolic blood pressure was around 120 mmHg, and
intraoperative systolic blood pressure remained at 100-130 mmHg. The
patient was urgently transferred to the intensive care unit (ICU) for
close observation. Approximately one hour after admission to the ICU,
the patient developed involuntary movements in the left upper limb,
suggestive of a seizure. Based on the assumption of an epileptic
seizure, 5 mg of diazepam was administered, which resulted in an
improvement in the level of consciousness (GCS E4V5M6). No further
obvious neurological abnormalities were observed. Subsequently,
levetiracetam administration was initiated from the first day after
surgery. Electroencephalography (EEG) performed on the second day after
surgery showed minimal significant findings. No seizures occurred
thereafter, and the patient was discharged on the 16th day after surgery
without any neurological complications.

\textbf{Discussion}

In this case, the patient developed unexplained postoperative DOC, which
was suspected to be an epileptic seizure based on the diagnostic and
therapeutic intervention. Epilepsy is considered one of the most serious
neurological disorders, affecting over 70 million people worldwide
{[}4{]}. Its incidence follows a bimodal distribution, with the highest
risk observed in infants and the elderly. Furthermore, it has been
pointed out that approximately 30\% of elderly-onset epilepsy cases
experience status epilepticus at the time of initial onset, and among
them, the frequency of NCSE is high {[}5{]}. NCSE is defined as a
condition characterized by non-convulsive clinical neurological symptoms
caused by EEG seizure activity lasting for more than 30 minutes {[}6{]}.
The symptoms of NCSE have been reported to manifest as altered
consciousness, in the form of confusion or coma, as well as language
impairment, myoclonus-like movements, anxiety, excitement, delirium and
extrapyramidal symptoms {[}7{]}. In this case, the patient initially
regained consciousness after completion of general anesthesia. However,
shortly thereafter, he experienced loss of consciousness that persisted
for more than 30 minutes. Although EEG could not be performed during the
episode of impaired consciousness, it is likely that the patient
experienced NCSE characterized by the predominant symptom of DOC. NCSE
is a condition that is often observed in patients with unexplained DOC
in whom no clear cause is identified by imaging. The diagnosis and,
hence, treatment of this condition, is often missed because it does not
present with obvious seizures. However, if treatment is delayed, it can
lead to irreversible brain damage. Therefore, early diagnosis and prompt
treatment are crucial {[}8{]}. The risk factors for the development of
NCSE include prodromal generalized tonic-clonic seizures, a history of
epilepsy, advanced age, female gender, and a history of brain injury.
Therefore, in the presence of any of these risk factors in a patient
with unexplained DOC, NCSE should be considered in the differential
diagnosis {[}9,10{]}. In this patient, there were no specific risk
factors except for advanced age, which made the diagnosis challenging.

The treatment of NCSE often involves the administration of
benzodiazepines, which have been found to be effective {[}11,12{]}. In
this case, significant improvement in consciousness was observed after
administration of diazepam. Other medications, such as phenytoin and
valproic acid, might also be considered in the treatment. Newer
antiepileptic drugs, such as levetiracetam, which have fewer side
effects and drug interactions, can also be used for the treatment of
NCSE {[}13{]}.

It is indeed rare to observe the onset of NCSE immediately after the
completion of general anesthesia for surgery. To our knowledge, there
have been a few reported cases of NCSE occurring after neurosurgical
procedures, but only one reported case of NCSE following non-cranial
surgery {[}14{]}. Our experience suggests that when organic causes for
post-anesthetic impaired consciousness are ruled out, NCSE should be
considered in the differential diagnosis. If feasible, immediate EEG
monitoring should also be considered to aid in diagnosis.

In this case, although a definitive diagnosis of NCSE could not be made
due to the unavailability of immediate EEG monitoring, improvement in
consciousness level immediately following the administration of diazepam
as a diagnostic and therapeutic intervention strongly suggested the
possibility of NCSE. Post-anesthetic DOC can often be attributed to
residual effects of anesthetic drugs, making it challenging to diagnose
NCSE. However, in elderly patients, NCSE should be considered in the
differential diagnosis of DOC. Fortunately, in this case, the patient
was managed without severe neurological complications.



\textbf{List of abbreviations}

DOC: disorder of consciousness

NCSE: non-convulsive status epilepticus

GCS: Glasgow Coma Scale

EEG: electroencephalogram

ICU: intensive care unit

\textbf{Declarations}

\textbf{Ethics approval and consent to participate}

Not applicable

\textbf{Consent for publication}

Written, informed consent was obtained from the patient for publication
of this case report and accompanying images.

\textbf{Availability of data and material}

Not applicable

\textbf{Competing interests}

The authors declare that they have no competing interests associated
with this manuscript.

\textbf{Funding}

None

\textbf{Authors' contributions}

YT contributed to the anesthesia management of the patient,
conceptualization of the case report, and writing of the original draft.
YI edited the manuscript. MT was the overall supervisor of this case.
All authors read and approved the final manuscript.

\textbf{Acknowledgements}

The authors would like to thank Forte Science Communications, Tokyo,
Japan, for English language editing.

\textbf{Authors' information}

\textbf{Affiliation}

Department of Anesthesiology

Tokyo Medical University

6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan

Yumi Tsuzuki, Yusuke Ishida, Mikiko Tomino

\textbf{References}

{[}1{]} Eapen BC, Georgekutty J, Subbarao B, Bavishi S, Cifu DX.
Disorders of Consciousness. Phys Med Rehabil Clin N Am. 2017;28:245-58.

{[}2{]} Karpenko A, Keegan J. Diagnosis of Coma. Emerg Med Clin North
Am. 2021;39:155-72.

{[}3{]} Amorim RL, Nagumo MM, Paiva WS, Andrade AF, Teixeira MJ. Current
clinical approach to patients with disorders of consciousness. Rev Assoc
Med Bras (1992). 2016;62:377-84.

{[}4{]} Thijs RD, Surges R, O'Brien TJ, Sander JW. Epilepsy in adults.
Lancet. 2019;393:689-701.

{[}5{]} Waterhouse EJ, DeLorenzo RJ. Status epilepticus in older
patients: epidemiology and treatment options. Drugs Aging.
2001;18:133-42.

{[}6{]} Cheng S. Non-convulsive status epilepticus in the elderly.
Epileptic Disord. 2014;16:385-94.

{[}7{]} Sutter R, R\selectlanguage{ngerman}üegg S, Kaplan PW. Epidemiology, diagnosis, and
management of nonconvulsive status epilepticus: Opening Pandora's box.
Neurol Clin Pract. 2012;2:275-86.

{[}8{]} Rossetti AO, Hirsch LJ, Drislane FW. Nonconvulsive seizures and
nonconvulsive status epilepticus in the neuro ICU should or should not
be treated aggressively: A debate. Clin Neurophysiol Pract.
2019;4:170-7.

{[}9{]} Dupont S. Non convulsive status epilepticus in the elderly.
Geriatr Psychol Neuropsychiatr Vieil. 2019;17:25-30.

{[}10{]} Woodford HJ, George J, Jackson M. Non-convulsive status
epilepticus: a practical approach to diagnosis in confused older people.
Postgrad Med J. 2015;91:655-61.

{[}11{]} Walker MC. Treatment of nonconvulsive status epilepticus. Int
Rev Neurobiol. 2007;81:287-97.

{[}12{]} Walker MC. Diagnosis and treatment of nonconvulsive status
epilepticus. CNS Drugs. 2001;15:931-9.

{[}13{]} Lee SK. Diagnosis and Treatment of Status Epilepticus. J
Epilepsy Res. 2020;10:45-54.

{[}14{]} Kim KO, Lee T, Kim T. Non-convulsive status epilepticus in the
immediate postoperative period following spine surgery -a case report.
Korean J Anesthesiol. 2021;74:541-5.

\textbf{Figure legends}

\textbf{Figure 1. Head computed tomography}

There was no evidence of intracranial hemorrhage.

\textbf{Figure 2. Head magnetic resonance imaging}

There were no findings indicating new-onset infarction.

\textbf{Key Clinical Message}

Disorder of consciousness can lead to irreversible sequelae without
proper intervention. Consequently, early diagnosis and treatment are of
paramount importance in patients with disorder of consciousness.

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