Presentation: onset and premorbid conditions

Reported presentations of perinatal FND varied widely, with functional seizures the most frequently reported FND subtype.

Around one-third of reported cases were of FND with onset preceding pregnancy. In this group, a subset of women experienced transient worsening of functional symptoms, often with resolution postpartum, and some women experienced FND (motor, visual and seizures) almost exclusively during pregnancy.^{Reference Lodge, Novak, Coebergh and Edwards19,Reference Pryse-Phillips and Yorkston36,Reference Muth53}

The second group, the largest represented in this review, comprised women with perinatal-onset FND. Notably, the third trimester, labour and postpartum were the most common periods for symptom onset in this group. Although this review does not shed light on why this is case, precipitating factors for FND identified in the literature, including pain, are likely relevant.^{Reference Pareés, Maja, Pires, Rubio-Agusti, Saifee and Sadnicka10,Reference Stone, Warlow, Deary and Sharpe11} Moreover, despite evidence not being available for FND populations, studies have linked perceived lack of autonomy or dissatisfaction with care during labour, sleep deprivation, fatigue, hormonal and weight changes, and adjustment to new parenthood in the postpartum period, with peri-labour dissociative experiences (including altered time perceptions and derealisation).^{Reference Choi and Seng13,Reference Zambaldi, Cantilino, Farias, Moraes and Sougey54,Reference Brockington55} These acute stress disorders and dissociative symptoms are more frequent in the cases of premature birth, prolonged, painful or complicated delivery, following emergency Caesarean section, where there is illness in the mother or the child, and with high levels of negative emotions during the pregnancy, including following perinatal loss.^{Reference Stadlmayr, Bitzer, Amsler, Simoni, Alder and Surbek56–Reference Armstrong, Hutti and Myers58}

Premorbid psychiatric and neurological conditions, and a history of adverse events, were present in nearly half of the cases of perinatal FND reported in this review. This is consistent with literature supporting adverse events as a risk factor for FND,^{Reference Ludwig, Pasman, Nicholson, Aybek, David and Tuck4–Reference Baker, Ben-Tovim, Butcher, Esterman and McLaughlin6} and an association between FND and mental health comorbidities.^{Reference Carle-Toulemonde, Goutte, Do-Quang-Cantagrel, Mouchabac, Joly and Garcin9} Of note, late pregnancy and the early postnatal period are also recognisable periods of recurrence of pre-existing psychiatric disorders, such as anxiety, psychosis and mood disorders,^{Reference Howard and Khalifeh12,Reference Paschetta, Berrisford, Coccia, Whitmore, Wood and Pretlove59} as well as an increased risk of disorders in individuals who hitherto have not suffered from mental illness, potentially representing a higher risk period for FND. Whether other modifiable factors, such as anticipatory fear about the delivery, also play a role in perinatal FND remains unclear.

Misdiagnosis and anti-seizure medication

Misdiagnosis of perinatal FND during pregnancy can be dangerous. Anti-seizure medications in women with functional seizures diagnosed incorrectly as epileptic seizures are potentially teratogenic,^{Reference Schechter, Kaminer, Grienenberger and Amat60} and women can be needlessly exposed to other risks, such as intravenous medications and admissions to intensive care units.^{Reference Dworetzky, Weisholtz, Perez and Baslet61} More than half of the reported cases of perinatal functional seizures received intravenous medication. The frequently acute and dramatic clinical presentations of pseudostatus epilepticus often pose diagnostic difficulties and likely account for these results. Stopping anti-seizure medications after initiation proved challenging in some,^{Reference Tomson, Battino and Perucca62} and women expressed the wish to terminate the pregnancy due to anxiety about teratogenicity.^{Reference McAuley, Patankar, Lang and Prasad63} It is important to proactively review anti-seizure medication prescribed to women without epilepsy or bipolar affective disorder, especially where teratogenic risks are known. Moreover, continuing anti-seizure medication at the expense of other treatments deprives women of potentially helpful treatments targeting functional seizures. Notably, cases where improvement was observed included those who had regular neuropsychiatric follow-up, psychotherapy and/or cessation of anti-seizure medication after diagnostic revision. The optimal management of pseudostatus epilepticus during the perinatal period requires close collaboration between the patient and family, perinatal teams, emergency care clinicians, neurologists and psychiatrists, and efforts to increase diagnostic awareness of FND. This also potentially reduces chances of prematurity from needlessly early delivery. Only 2 out of 21 cases reporting birth outcomes mentioned complications.^{Reference Bryant, Wharton and Alexander43,Reference Załuska, Zurko, Kuroń, Jakiel and Dudel51} This is consistent with data from an abstract that did not find differences in prenatal, labour or neonatal outcomes, namely increase in neonatal deaths or congenital malformations, between 10 women with epilepsy, 9 with functional seizures and 25 healthy controls (no individual data regarding these women were provided).^{Reference Fertig, Alexandra, Moreno, Smith and Baraban64}

Physical precipitants of functional motor symptoms

Functional motor symptoms almost exclusively occurred during the third trimester, labour and postpartum period, and often followed spinal and epidural anaesthesia. We hypothesise that physical precipitants of functional motor symptoms, such as altered sensory feedback from anaesthesia, could have produced a mismatch between expectations and sensory input.^{Reference Edwards, Adams, Brown, Pareés and Friston65} This would be consistent with evidence that medical and surgical interventions are risk factors for functional movement disorders,^{Reference Mason, Renée, Marples, McWhirter, Carson and Stone8,Reference Pareés, Maja, Pires, Rubio-Agusti, Saifee and Sadnicka10,Reference Stone, Warlow, Deary and Sharpe11} which may be in keeping with a slightly higher rate of Caesarean compared with vaginal deliveries in these FND cases. In addition, we can hypothesise that clinicians may have been more likely to recommend elective Caesarean for women experiencing FND symptoms such as severe bilateral leg weakness, or this may have been urgently recommended because of ongoing symptoms such as dissociative events, fatigue or new-onset weakness. We found fewer case reports of functional motor symptoms than functional seizures, even though in practice the frequency appears to be similar. This may just reflect the epidemiology of these subtypes, with functional seizures having a peak onset in the late teens/early 20s, whereas functional motor symptoms have a peak onset in the late 30s.^{Reference Lidstone, Costa-Parke, Robinson, Ercoli and Stone3}

Non-pharmacological interventions

Psychological and physiotherapy interventions, a mainstay of FND treatment, were used in six reported cases, with improved outcomes in four.^{Reference Devireddy and Sharma31,Reference Herr, Hatch, Sephien and Hanna34–Reference Pryse-Phillips and Yorkston36,Reference García, Vargaz and Lopez45,Reference Dogan50} They remain largely unexplored in this group despite evidence for FND in general.^{Reference Gutkin, McLean, Brown and Kanaan66,Reference Nielsen, Buszewicz, Stevenson, Hunter, Holt and Dudziec67}

Limitations

Our findings have significant limitations. The existing literature is partially populated by conference abstracts, and data were mostly drawn from case reports where reporting and selection bias are likely to be high. It is likely, for example, that authors would be drawn to report new cases of FND during pregnancy, whereas cases of women with prenatal FND whose symptoms had improved or stayed stable are likely to be underrepresented. Variable follow-up data and lack of information on symptom trajectory across the case reports means that long-term outcomes are difficult to determine. Misdiagnosis is a possibility since 20 of the 36 studies were published before 2013, when the new DSM-5 classification of FND defying the traditional mind–body dualistic way of thinking and approach was published. So, some of the diagnostic methods in these studies do not align with current standards for both diagnosis and treatment and current Bayesian understanding of brain–body networks.^{Reference Aybek and Perez68} Equally, four cases described signs such as ‘la belle indifference’, which have already proved not to be discriminative.^{Reference Stone, Smyth, Carson, Warlow and Sharpe69} The presence of a normal EEG during episodes of functional seizures counterbalances this concern for at least some reports.

Clinical and research implications

These cases demonstrate the strikingly limited literature on perinatal FND, which does not allow us to answer many of the important questions regarding FND and the perinatal period.

However, this review provides a tentative starting point for well-designed cohort studies. Until then, the management of perinatal FND should follow the standard of care of other FNDs, with the necessary adaptions for the patients’ state. Early diagnosis, communication and multidisciplinary treatment of FND are vital.^{Reference Hallett, Aybek, Dworetzky, McWhirter, Staab and Stone2} Involvement of families and destigmatisation about the condition are key to progress in this area. Choices of delivery and anaesthetic methods are to be taken by obstetric teams together with the patient, on an individual basis, but currently there are no known contraindications for vaginal or Caesarean delivery.

Future studies should explore the role of perceptions of pregnancy and motherhood in relation to FND symptom onset and trajectory. A greater understanding of the relationship between common psychiatric comorbidities during the postnatal period, including dissociation, postpartum depression, PTSD^{Reference Paschetta, Berrisford, Coccia, Whitmore, Wood and Pretlove59} and FND, would benefit the development of joint care pathways and preventive strategies. For women with previous miscarriage or stillbirth, support after perinatal loss may help reduce vulnerability.^{Reference Spinelli70} In women with pre-existing FND, more research into the course of symptoms throughout the perinatal period is needed. Particularly, it remains unknown which women are at higher risk of complications of their FND or immediate relapse postpartum, as well as those at risk of new onset of perinatal FND. Our personal experience is that many women with pre-existing FND find that their neurological symptoms improve during pregnancy, especially during the second trimester. The role of fatigue in labour protraction or arrest in patients with FND also remains to be explored, as well as considerations of previous obstetric adversities (including infertility and assistive reproductive technology) as potential risk factors for perinatal-onset FND.

Lastly, in women with FND the desire to raise their own family is often undermined by concerns about physical and emotional repercussions for the mother and the hypothetical interference of FND symptoms in the ability to take care of the newborn. Women also express other worries, such as fear of passing on FND to future generations and concerns over iatrogenic risks of certain pharmacological therapies and the need to interrupt certain treatments. It is likely that FND itself might affect sexual function and libido for some women, which can affect conception. These concerns warrant investigation in forthcoming prospective studies. Collaborative efforts among neurological, psychiatric and perinatal care teams will be key to produce guidance that supports women with FND in their pregnancy and delivery planning.