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Table of Contents    
Year : 2018  |  Volume : 66  |  Issue : 6  |  Page : 1629-1633

Status epilepticus related to pregnancy: Devising a protocol for use in the intensive care unit

Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India

Date of Web Publication28-Nov-2018

Correspondence Address:
Dr. Ashalatha Radhakrishnan
Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram - 695 011, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.246279

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 » Abstract 

Background: Status epilepticus (SE) related to pregnancy is rare and carries a significant risk to both the mother and the fetus.
Objectives: We conducted this study to devise a protocol for the management of SE related to pregnancy in a cohort of female patients admitted with SE during pregnancy.
Materials and Methods: All women who developed SE related to pregnancy (gestation, labor, and puerperium) between January 2000 and December 2016 were included. Data was collected using a structured proforma.
Results: There were 17 women who had SE related to pregnancy, of whom 10 had refractory SE. The various causes of refractory SE were eclampsia (N = 2), posterior reversible encephalopathy syndrome (PRES) due to various causes other than eclampsia (N = 3), cortical venous thrombosis (CVT) [N = 3], subarachnoid hemorrhage (SAH) [N = 1], and N-methyl-D-aspartate (NMDA) receptor antibody-mediated encephalitis (N = 1). Six out of 10 women with refractory SE (60%) and five out of 10 fetuses (50%) had a good outcome.
Conclusion: There is a dearth of literature with regards to SE related to pregnancy and little or no guidelines exist for its management. Awareness about the diverse etiologies other than eclampsia is important. A protocol-based approach to the diagnosis and management of SE is necessary to ensure best outcomes.

Keywords: Eclampsia, pregnancy, protocol, refractory, status epilepticus
Key Message: Very few guidelines exist for the management of status epilepticus (SE) related to pregnancy. Awareness during pregnancy regarding the diverse etiologies other than eclampsia, that may lead to the development of SE, and a protocol-based approach to its diagnosis and management are necessary to ensure a good outcome.

How to cite this article:
Rajiv KR, Menon RN, Sukumaran S, Cherian A, Thomas SV, Nair M, Radhakrishnan A. Status epilepticus related to pregnancy: Devising a protocol for use in the intensive care unit. Neurol India 2018;66:1629-33

How to cite this URL:
Rajiv KR, Menon RN, Sukumaran S, Cherian A, Thomas SV, Nair M, Radhakrishnan A. Status epilepticus related to pregnancy: Devising a protocol for use in the intensive care unit. Neurol India [serial online] 2018 [cited 2022 May 26];66:1629-33. Available from: https://www.neurologyindia.com/text.asp?2018/66/6/1629/246279

Status epilepticus (SE) in pregnancy is rare and may occur during gestation, labor, or puerperium. From the limited literature data available, in addition to eclampsia, other conditions such as viral encephalitis, systemic lupus erythematosus, cavernoma, reversible cerebral vasoconstriction syndrome, pyridoxine deficiency, and N-methyl-D-aspartate (NMDA) receptor antibody mediated autoimmune encephalitis have been implicated to cause SE in pregnancy.[1],[2],[3],[4],[5],[6] In our recently published data, we found six cases of posterior reversible encephalopathy syndrome (PRES) due to diverse etiologies other than eclampsia.[7] The treatment of SE in pregnancy is a challenge and the teratogenicity of first or second-line antiepileptic drugs (AEDs) is well-known; little is known, however, regarding the safety and tolerability of anesthetic agents used in the management of refractory status epilepticus (RSE).

We conducted this study, to thoroughly scrutinize and analyze all the cases of SE in pregnancy to devise a protocol for its management which is lacking in literature.

 » Materials and Methods Top

We identified from our prospectively maintained records, a cohort of women who had SE related to pregnancy (during gestation, labor, or puerperium) between January 2000 and December 2016, admitted to the intensive care unit (ICU) of our institute, a tertiary referral center with a comprehensive epilepsy care program. All data were collected using a structured proforma and analyzed in detail. We made literature-based variations in the general guidelines for management of SE, which has been validated and published earlier by our group, to cater to this cohort of patients who developed “pregnancy related refractory SE.”[8]


“SE” was defined as abnormally, prolonged seizures, lasting for at least 5 min, resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of failure mechanisms.[9]

“Refractory SE” was defined as SE that does not respond to the initial anticonvulsant treatment with at least one first line intravenous (IV) antiepileptic drug (AED), benzodiazepines, and one or more of second line AEDs, and requiring general anesthetic agents, regardless of the delay since the onset of the seizure.[10]

“Puerperium” was defined as a period of 1 week after delivery of a viable or a nonviable fetus.


The etiology of seizures was classified according to the International League Against Epilepsy (ILAE) recommendations[11] into acute symptomatic, progressive symptomatic, remote symptomatic, or of unknown etiology.


Maternal outcomes were assessed using the functional independence measure (FIM) outcome score and the Modified Rankin scale (mRS).[12],[13] The patients were grouped based on the condition at the time of discharge into having a “good outcome” (FIM score 4–7; mRS 0–2) and a “poor outcome” (FIM score 1–3; mRS >3). The fetal outcome after delivery was divided into “normal alive fetus without any complications” (Category-1) and “fetal death or perinatal complications needing admission to the neonatal intensive care unit [ICU]” (Category-2).

 » Results Top

During the 16-year study period spanning two decades, a total of 348 SE events were recorded in 294 patients. In them, there were 17 women who developed SE related to pregnancy, of which two women each developed SE in the first and third trimester respectively, and the remaining 13 women developed SE in the puerperal period. The mean age of the cohort was 23.69 ± 3.03 years. Ten women had refractory SE, among whom two women with eclampsia were in the third trimester of pregnancy and the remaining eight women were in the puerperal period. Continuous electroencephalogram (EEG) monitoring was done in all cases. Non-convulsive status epilepticus (NCSE) was detected in two cases, one case of posterior reversible encephalopathy syndrome (PRES) and one case of N-methyl-D-aspartate (NMDA) receptor antibody mediated encephalitis.

Etiology and outcome of refractory status epilepticus in pregnancy

The etiology of RSE was acute symptomatic in all cases (N = 10). The various causes of refractory SE were eclampsia (N = 2), PRES due to various causes other than eclampsia (N = 3), cortical venous thrombosis (N = 3), subarachnoid hemorrhage (SAH) [N = 1], and NMDA receptor antibody mediated encephalitis (N = 1).

Six out of 10 (60%) women had a good outcome. Among the cases with a poor outcome, there were two cases of cortical venous thrombosis (CVT) and one case each due to PRES and SAH, respectively. Five out of 10 (50%) fetuses had good outcomes (Category 1). The major fetal complications noted were low birth-weight in four (23%) fetuses, respiratory distress in two (11%) fetuses, anoxic brain injury in one (5%) fetus, and grade-II intraventricular hemorrhage in one (5%) fetus.

Treatment of refractory status epilepticus in pregnancy

The first line agent for treatment of SE was lorazepam in eight patients (80%) and midazolam in two patients (20%). The first line AED used was fosphenytoin in seven patients (70%) and phenobarbitone in three (30%) patients. The second line AEDs used were phenobarbitone and levetiracetam in three patients (30%) each, while fosphenytoin and sodium valproate were used in two patients (20%) each.

Among the anesthetic agents used for management of RSE, midazolam alone was able to control SE in four patients, and propofol alone in three patients. In the remaining three patients with refractory SE, a combination of midazolam plus thiopentone was used in two patients, and midazolam plus propofol was used in one patient. The two patients who developed RSE in the third trimester as a result of eclampsia were initially given magnesium sulfate based on the Pritchard regimen,[14] and fosphenytoin followed by phenobarbitone and propofol were administered subsequently for controlling SE. The adverse effects related to the use of intravenous (IV) anesthetic agents were hypotension (N = 4), bradycardia (N = 2), and paralytic ileus (N = 1). The treatment of refractory SE is summarized in [Table 1].
Table 1: Treatment of refractory status epilepticus in pregnancy

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 » Discussion Top

Majority of the women who develop SE related to pregnancy are managed by the obstetrician. The neurologist is only called into action in the refractory cases. This study was done with the aim to come up with a protocol for this specific entity, often overlooked, for which little or no guidelines exist so far, i.e., pregnancy related SE, which causes a significant morbidity and mortality to the mother and fetus.

We encountered 17 patients, of which 10 patients had refractory SE related to pregnancy. The important finding we noticed was that eclampsia accounted for only 20% of all cases. Moreover, three patients had PRES like changes on magnetic resonance imaging (MRI) in the absence of eclampsia. Amongst the remaining five patients, there were three cases with CVT, and one case each, respectively, due to SAH and NMDA-R antibody mediated encephalitis. The patient with NMDA-R encephalitis had a flare up in the postpartum period; she was initially misdiagnosed as postpartum psychosis and presented with behavioral changes related to NCSE. The observations from our study, in comparison with the previous reports, are summarized in [Table 2].
Table 2: Comparison of current study with previous literature on treatment of refractory status epilepticus in pregnancy

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The management of SE during pregnancy depends on various factors such as the period of gestation, etiology, and associated co-morbidities. In general, termination of pregnancy is the rule in cases of refractory SE, as recurrent seizures can cause significant risk to both the mother and fetus. With regards to the etiology, various trials have shown that magnesium sulfate is the treatment of choice for eclampsia in pregnancy.[15],[16] About 10% of patients with eclampsia continue to have seizures despite administration of magnesium. In such cases, in various case reports, anesthetic agents such as propofol have been successfully tried.[17],[18],[19],[20] Other than in eclampsia, there are no established guidelines for the management of pregnancy related SE. The main aim in such situations should be to terminate SE. The harmful effects of prolonged SE are more deleterious than the potential teratogenic effects of IV anesthetic agents. Regarding initiation of immunotherapy in patients with autoimmune encephalitis presenting as refractory SE in pregnancy, although there are no established guidelines, IV methyl prednisolone can be considered as first-line treatment. In refractory cases, in view of hemodynamic fluctuations in pregnancy, immunoglobulin (IVIG) can be considered as a safer option than plasma exchange.

In our study, refractory SE due to eclampsia, where magnesium sulfate had failed, was controlled with propofol. We followed our uniform SE protocol,[8] for management of cases of non-eclamptic refractory SE with minor modifications as and when needed to ensure the best outcomes possible in the mother and fetus. Majority of the patients were administered a loading dose of phenytoin as a first line AED for SE from a nearby primary or secondary health care center prior to their referral to our center; and, the second line AEDs most commonly used were levetiracetam and phenobarbitone. In our recently published data, we observed that with regard to the use of second line AED in SE, levetiracetam showed a rising trend, being the agent of choice in two-thirds of patients, while as a result of high risk of teratogenicity, the use of valproate might have been avoided.[7] The IV anesthetic agents used were midazolam, followed by propofol and thiopentone. The major adverse effects related to the use of anesthetic drugs were averted by the virtue of intensive monitoring in the ICU. Our uniform protocol driven management resulted in a good outcome in two-thirds of all cases. We did not encounter any maternal or fetal deaths. Our protocol for management of SE is summarized in [Figure 1].
Figure 1: Protocol for management of status epilepticus in pregnancy

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Our study had certain limitations that the cohort was prospectively collected but retrospectively analyzed. Since there were no existing guidelines, each of the members of the cohort was treated with the uniform guidelines existing for any SE patient and further modifications were incorporated to tailor to the needs of each of the pregnant patients. Only such studies would help us in drawing conclusions. These can also inspire prospective studies in the future, since randomized controlled trials may be difficult in a situation like SE in pregnancy.

In conclusion, there is a dearth of evidence on the treatment of SE related to pregnancy and hardly any guidelines exist. Awareness regarding diverse etiologies other than eclampsia is important during pregnancy. A protocol-based approach to diagnosis and management of SE is necessary to ensure the best outcomes.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 » References Top

Lu YT, Hsu CW, Tsai WC, Cheng MY, Shih FY, Fu TY, et al. Status epilepticus associated with pregnancy: A cohort study. Epilepsy Behav 2016;59:92-7.  Back to cited text no. 1
Gunduz A, Beskardes AF, Kutlu A, Ozkara C, Karaagac N, Yeni SN. Herpes encephalitis as a cause of nonconvulsive status epilepticus. Epileptic Disord 2006;8:57-60.  Back to cited text no. 2
Engelhardt K, Trinka E, Franz G, Unterberger I, Spiegel M, Beer R, et al. Refractory status epilepticus due to acute hepatic porphyria in a pregnant woman: Induced abortion as the sole therapeutic option? Eur J Neurol 2004;11:693-7.  Back to cited text no. 3
Legriel S, Merceron S, Pico F, Cordoliani YS, Bedos JP. A rare cause of status epilepticus. Intensive Care Med 2011;37:1718-9.  Back to cited text no. 4
Aladdin Y, Gross DW. Refractory status epilepticus during pregnancy secondary to cavernous angioma. Epilepsia 2008;49:1627-9.  Back to cited text no. 5
Schulze-Bonhage A, Kurthen M, Walger P, Elger CE. Pharmacorefractory status epilepticus due to low vitamin B6 levels during pregnancy. Epilepsia 2004;45:81-4.  Back to cited text no. 6
Rajiv KR, Radhakrishnan A. Status epilepticus in pregnancy: Etiology, management, and clinical outcomes. Epilepsy Behav 2017;76:114-9.  Back to cited text no. 7
Hassan H, Rajiv KR, Menon R, Menon D, Nair M, Radhakrishnan A. An audit of the predictors of outcome in status epilepticus in a resource-poor country: A comparison with developed countries. Epileptic Disord 2016;18:163-72.  Back to cited text no. 8
Al-Mufti F, Claassen J. Neurocritical care: Status epilepticus review. Crit Care Clin 2014;30:751-64.  Back to cited text no. 9
Shorvon S, Ferlisi M. The outcome of therapies in refractory and super-refractory convulsive status epilepticus and recommendations for therapy. Brain 2012;135:2314-28.  Back to cited text no. 10
Guidelines for epidemiologic studies on epilepsy. Commission on Epidemiology and Prognosis, International League Against Epilepsy. Epilepsia 1993;34:592-6.  Back to cited text no. 11
Keith RA, Granger CV, Hamilton BB, Sherwin FS. The functional independence measure: A new tool for rehabilitation. Adv Clin Rehabil 1987;1:6-18.  Back to cited text no. 12
Farrell B, Godwin J, Richards S, Warlow C. The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: Final results. J Neurol Neurosurg Psychiatry 1991;54:1044-54.  Back to cited text no. 13
Pritchard JA, Cunningham FG, Pritchard SA. The Parkland Memorial Hospital protocol for the treatment of eclampsia: Evaluation of 245 cases. Am J Obstet Gynaecol 1984;148:951-63.  Back to cited text no. 14
Duley L. Magnesium sulphate in eclampsia. Eclampsia Trial Collaborative Group. Lancet 1998;352:67-8.  Back to cited text no. 15
Magpie Trial Follow-Up Study Collaborative Group. The Magpie Trial: A randomised trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for children at 18 months. BJOG 2007;114:289-99.  Back to cited text no. 16
Hilton G, Andrzejowski JC. Prolonged propofol infusions in pregnant neurosurgical patients. J Neurosurg Anesthesiol 2007;19:67-8.  Back to cited text no. 17
Dubey D, Kalita J, Misra UK. Status epilepticus: Refractory and super-refractory. Neurol India 2017;65, Suppl S1:12-7.  Back to cited text no. 18
Singh SP, Sankaraneni R, Antony AR. Evidence-based guidelines for the management of epilepsy. Neurol India 2017;65, Suppl S1:6-11.  Back to cited text no. 19
Dam AK, Mishra JC, Shome PK. Treatment of refractory seizures in eclampsia with propofol - a case report. Indian J Anesth 2004;48:314-5.  Back to cited text no. 20


  [Figure 1]

  [Table 1], [Table 2]

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