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NI FEATURE: THE EDITORIAL DEBATE I-- PROS AND CONS
Year : 2018  |  Volume : 66  |  Issue : 6  |  Page : 1590-1592

Status epilepticus related to pregnancy


Department of Neurology, Seth G.S. Medical College and K.E.M. Hospital, Parel, Mumbai, Maharashtra, India

Date of Web Publication28-Nov-2018

Correspondence Address:
Dr. Sangeeta Ravat
Department of Neurology, Seth G.S. Medical College and K.E.M. Hospital, Parel, Mumbai - 400 012, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.246226

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How to cite this article:
Ravat S, Desai K, Shah M. Status epilepticus related to pregnancy. Neurol India 2018;66:1590-2

How to cite this URL:
Ravat S, Desai K, Shah M. Status epilepticus related to pregnancy. Neurol India [serial online] 2018 [cited 2018 Dec 10];66:1590-2. Available from: http://www.neurologyindia.com/text.asp?2018/66/6/1590/246226




The management of women with epilepsy (WWE) is very challenging, especially taking into account the risk of teratogenicity to the foetus as well as the associated maternal morbidity. The first conclusive report of the teratogenicity related to anticonvulsants was published in The Lancet by Meadow in 1968.[1] This study reported the occurrence of hare lip, cleft palate and other abnormalities in six children whose mothers were taking phenytoin, barbiturate and troxidone. Even after five decades, establishing the delicate balance between ensuring seizure control in the mother and achieving a good outcome for the foetus remains an elusive endeavour, with the efforts befuddled by ethical and medical challenges, despite a lot of literature being published on this matter. Most of the literature published pertaining to epilepsy and pregnancy, as well as to clinical practice has been focussed on teratogenicity and foetal outcomes, with very little consideration being given to the maternal outcomes. The purpose of this dialogue, however, is on a more specific issue pertaining to WWE, which is the management of status epilepticus (SE) in pregnancy. There is a shocking dearth of literature on the prevalence and etiological factors related to the management of SE in pregnancy. Apart from some data published by the European Registry of Antiepileptic Drugs and Pregnancy (EURAP), as an initiative of the International Registry of Antiepileptic Drugs and Pregnancy, and a couple of other case series published by other groups, the only literature available pertaining to this extremely vexing issue is in the form of isolated case reports. The incidence rate of SE related to pregnancy, based upon the EURAP registries, is in the range of 0.6-1.8 percent out of all registered pregnancies.[2],[3] The Indian studies have tried to focus on status epilepticus in a holistic and retrospective manner without focusing on pregnancy.[4],[5]

Treating epilepsy in pregnancy is challenging due to the physiological changes occurring in the mother affecting the anti-epileptic drug (AED) concentration and enhancing the risk of teratogenicity. Epilepsy in pregnancy is even more difficult to manage if the patients present with SE during pregnancy. When it comes to status epilepticus, maternal health takes precedence over foetal health. It is really a commendable effort by Rajiv et al., for being the first ones to devise a structured protocol for managing pregnant women with SE.[6] The only other major published study that looks at SE in pregnancy, published by Lu et al.,[7] showed that 2.1 percent of cases of SE out of the total SE cohort were related to pregnancy. This figure is significantly low, when compared to the 5 percent figure published by the authors in their previous study.[8] However, the Chinese group excluded cases of eclampsia, which has been one of major causes of seizures and SE in pregnancy.[7] The authors of the study in focus speculate that this discrepancy is due to there being a better referral system in place at their institute and the fact that all pregnancy related cases of SE were co-managed by the neurologists.[6] Although the EURAP includes cases from the Kerala Registry of Epilepsy and Pregnancy (KREP) as well, the inclusion criteria established by them are likely to miss out on many important causes of SE related to pregnancy. This is because many pregnancy related causes of epilepsy, like posterior reversible encephalopathy syndrome (PRES), cortical venous thrombosis (CVT), subarachnoid haemorrhage (SAH) and even autoimmune encephalitis (AIE), have been left out. The key point in the entire discussion has been that most of the above-mentioned causes are in women who per se are not WWE. In keeping with the spirit of this point, it is important to note that 15 of the 17 cases from the study in focus were women who were not having epilepsy prior to pregnancy. The authors highlight that not all cases of PRES had an underlying hemodynamic cause, with septicaemia also being equally culpable. The authors of the study have divided the cases of SE into the ‘Remote SE’ and the ‘Acute SE’ groups,[6] with emphasis on the need to cast a wider net in managing the Acute SE cases. The 2 cases of the Remote SE group were structural epilepsies with a history of poor anti-epileptic drug (AED) compliance, which points to the importance of ensuring an adequate compliance. In terms of the etiological profile, their findings were similar to the study by Lu et al.[6] Another Chinese study highlights four cases[9] of WWE who lapsed into SE. Three of four cases had successfully tapered off valproic acid prior to conception in order to avoid teratogenicity, but they landed up with SE during pregnancy, despite being fully compliant to the new AED regimen. This emphasizes the fact that the patients who are well controlled with valproate should be continued at a low dosage of valproate during pregnancy in order to avoid SE. In the EURAP study of 2006, it has been highlighted that deterioration of seizure control occurred equally in the second and third trimesters, and episodes of status epilepticus occurred evenly throughout pregnancy. So, it is important to closely monitor the patients for their AED levels and dosage throughout the pregnancy and not only in the third trimester. It is commendable that the authors’ data of nearly 16 years had only two cases of remote SE, that too due to non-compliance of AED, which reflects an astute management of AED during pregnancy.

This brings us to the main matter at hand which is that there have been no publications or consensus about the management of SE in this group of patients before the publication of the current study in focus. Even after the recent revision[10] of the clinical definition of SE and its types, guidelines for the management of epilepsy have not really witnessed a seismic change. There have been revisions in the definitions for refractory and super refractory SE,[10] and the entry of levetiracetam as a second line AED has been duly noted with some data on the efficacy of lacosamide as an alternative AED, but as far as the anaesthetic agents go, the armamentarium has not really changed. This has been aptly highlighted by the authors as well, but what is vital to note is that the optimum and timely use of general anaesthesia (GA) has been found to be necessary from time-to-time. The authors share their experience with the anaesthetic agents in the management of cases with non-convulsive SE (NCSE) as well as convulsive SE. The use of continuous electroencephalogram (EEG) monitoring is advisable in all cases. It has been pointed out that the use of valproic acid as a second line AED is recommended in extreme cases. Another point put forth by them was that there was the need to augment the time-tested Pritchard regimen in the cases who developed eclampsia despite being on second line AEDs and even anaesthetic agents, for achieving an optimum outcome in as many as 10 percent cases of eclampsia. The authors recommend that termination of pregnancy must be considered in all cases of refractory as well as super-refractory SE and also in the cases where teratogenic agents have been administered. More clarity on the execution of this delicate matter would be welcome as the pro-active management of termination of pregnancy in cases other than eclampsia is laden with potential medicolegal dilemmas.

In the study in focus,[6] the authors’ outcomes in the cases of pregnant mothers have been superior to that of Lu et al.[7] who report a 28 percent (2 out of 7 patients) mortality. The authors in the present study have followed up the mothers until 1 year after delivery with objective outcome parameters. 8 out of 17 (43 percent) cases had a poor foetal outcome, of which 5 were those in mothers with refractory SE, where the use of intravenous anaesthetics could have been deemed to be the culpable factor. The other 3 cases with a poor foetal outcome were likely to be secondary to the underlying aetiology of SE in the mother rather than to the management of SE.[6] The authors do not report the occurrence of any still births compared to the forty percent (2 out of 5 patients) rate reported by Lu et al.[7] The EURAP registry reports only one case of stillbirth, which was secondary to convulsive status epilepticus. In the EURAP registry, three off-springs, born to women who developed status epilepticus during pregnancy, were diagnosed with major congenital malformations (MCM). The authors do not report any MCM (which was focused upon in the study by Thomas et al.,[11] but this might have been due to the fact that the causes of SE in both the registries, although mutually inclusive, were vastly different.

Finally, to conclude, we welcome this much needed data and protocol for the management of SE in pregnancy as it can streamline and systematize the management of an extremely challenging entity. The authors have done a very meticulous data collection over 16 years and their analysis of the data is well standardized with the appropriate use of scales and outcome parameters. We fully support the need for an early involvement of the neurologist in decision making and management, as many of these cases probably remain under the care of the obstetricians until it is too late. Lastly, one critical comment, which the author also makes, would be related to the small sample size of the study in focus. Combining all the cases published till date, there is still lack of data based upon which unequivocal conclusions regarding the statistically significant and key factors determining the outcome may be established, and on the basis of which it may be possible to comment upon the efficacy of the treatment parameters. Another critical comment would be regarding the authors’ suggestion on medical termination of pregnancy in the cases of SE in the first and second trimester, as there is lack of data on foetal outcomes to support this, especially in those cases falling in the weeks 21-24 of gestation, where the current laws on medical termination of pregnancy could make the procedure a medicolegal issue. We hope that this motivates other groups to pool in more data as it would only add further information and input to the good work done by this group. The framework of the study in focus establishes the background for more prospective studies to be conducted in order to obtain additional data to support this protocol.



 
  References Top

1.
Meadow SR. Anticonvulsant drugs and congenital abnormalities. Lancet 1968;2:1296.  Back to cited text no. 1
    
2.
Battino D, Tomson T, Bonizzoni E, Craig J, Lindhout D, Sabers A, et al. Seizure control and treatment changes in pregnancy: Observations from the EURAP epilepsy pregnancy registry. Epilepsia 2013;54:1621-27.  Back to cited text no. 2
    
3.
EURAP Study Group. Seizure control and treatment in pregnancy: Observations from the EURAP epilepsy pregnancy registry. Neurology 2006;66,354-60.  Back to cited text no. 3
    
4.
Dubey D, Kalita J, Misra UK. Status epilepticus: Refractory and super-refractory. Neurol India 2017;65:S12-S17.  Back to cited text no. 4
[PUBMED]  [Full text]  
5.
Rajiv KR, Radhakrishnan A. Status epilepticus in pregnancy: Etiology, management, and clinical outcomes. Epilepsy Behav 2017;76:114-19.  Back to cited text no. 5
    
6.
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.  Back to cited text no. 6
  [Full text]  
7.
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. 7
    
8.
Hassan H, Rajiv KR, Menon R, Menon D, Nair M, Radhakrishnan A. An audit of the predictors of outcome in status epilepticus from a resource-poor country: A comparison with developed countries. Epileptic Disord Int Epilepsy J Videotape 2016;18:163-72.  Back to cited text no. 8
    
9.
Trinka, E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, Shorvon S, et al. A definition and classification of status epilepticus-Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia 2015;56,1515-23.  Back to cited text no. 9
    
10.
Wu M, Hao N, Yan B, Chi X, Zhou D. Status epilepticus in pregnant women with epilepsy after valproate adjustment: A case series. Seizure 2016;43:39-41.  Back to cited text no. 10
    
11.
Thomas SV, Jose M, Divakaran S, Sankara Sarma P. Malformation risk of antiepileptic drug exposure during pregnancy in women with epilepsy: Results from a pregnancy registry in South India. Epilepsia 2017;58:274-81.  Back to cited text no. 11
    




 

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