Myelomeningocele, new insights and better outcome in the era of fetal surgery

Myelomeningocele (MMC) is a complex open neural tube defect of the spinal cord caused by failure to fuse of the neural tube early in gestation. Leakage of cerebrospinal fluid (CSF) through the defect is thought to cause the brainstem and cerebellum to descend through the foramen magnum known as Chiari II or Arnold Chiari Malformation (ACM). This descend of brainstem and cerebellum causes obstruction for the CSF flow resulting in hydrocephalus. A more late complication seen in children born with MMC is tethering of the spinal cord at the site of surgical repair known as a form of secondary tethered spinal cord syndrome (TSC).
Survival rates in children with MMC changed only in the second halve of the 20st century with advances in surgery and mainly in the treatment of hydrocephalus. Survival increased but so did the number of severely impacted MMC patients. In the two most recent decades two important developments took place in MMC; active termination of pregnancy in the majority of MMC-pregnancies in countries like the Netherlands to prevent the often severe prognosis on the one hand and fetal surgery to close the defect during pregnancy in order to improve postnatal outcome on the other.
An RCT in the USA showed that in a select group of MMC pregnancies, the need for a CSF diverting shunt halves by performing fetal surgery. This constitutes a major indication for us to undergo the transition to a fetal surgery centre.
Even though the benefits of open fetal in MMC for the foetus are well-established, long-term data on especially tethered spinal cord are eagerly awaited.

This dissertation is on the impact of MMC, the role of fetal surgery, the importance of well-informed counseling and finally on simulation models to improve the technique of fetal surgery for MMC.
Chapter 1 provides an introduction on MMC followed by an overview of the current outcome on a cohort of MMC patients in our institution which will also serve as a historical cohort for comparison with fetal surgery cases in the near future in Chapter 2. The outcome is comparable with the literature apart from a relatively low rate of surgical untethering. Hydrocephalus is highly prevalent in postnatal treated MMC patients. In this study as in much of the literature, it is correlated with a low cognitive function.
Chapter 3 shows the results of a study performed on the same cohort of MMC patients we published on 10 years ago when they were newborns;. The study showed that patients' lives were affected in many domains. All patients were capable of effective communication, irrespective of severity of MMC. Overall, our data show that in newborn MMC patients future unbearable suffering with respect to pain, mobility, cognition and communication is hard to predict and may not always occur.
Chapter 4 covers a worldwide survey we performed amongst neurosurgeons showing diversity in the management of patients with MMC. In addition, significant diversity remains regarding fetal surgery for MMC closure. We feel that centralization of prenatal treatment to dedicated tertiary centres, as well as the use of sophisticated training models, may help overcome the most commonly cited objection to the implementation of prenatal closure, namely the overall limited caseload.
The meta-analysis and systematic review in Chapter 5 shows that the cumulative incidence and relative risk of TSC are increased in the prenatal closure group compared to the postnatal group in MMC patients. We conclude that in order to improve counselling on and outcome of MMC more long-term data on TSC after fetal closure for MMC is needed.
Chapter 6 describes the position of fetoscopic surgery for MMC as opposed to open fetal surgery. Open fetal surgery for MMC has become a widespread treatment option and in pursuit of minimizing its maternal risks, fetoscopic techniques are being explored. This created an expanding but fragmented field in which the optimal fetoscopic technique is yet to be determined. An RCT like the one for open fetal surgery is unlikely to ever take place and we suggest gathering data from high‐quality international registries with standardized outcomes to be a valuable alternative. In the absence of high-quality evidence, we emphasize the importance of careful and balanced in‐depth counselling taking in consideration individual risks and benefits for every patient.
Finally, in Chapter 7 we demonstrate a realistic simulator for the training of fetoscopic myelomeningocele surgery to provide a training opportunity for centres that are starting a fetoscopic MMC repair program as well as for more advanced centers to maintain their skills. It is the first simulation model with adjustable spinal defect and placental localisation. Further objective validation is required, but the potential for using this model in preoperative planning and in obtaining surgical skill is promising.
In the general discussion in Chapter 8, we elaborate on the important role of well-informed counselling in order to be able to decide upon terminating or continuing a MMC pregnancy and to be able to choose between fetal or postnatal surgery. More solid data will improve counselling. Using realistic simulation models may improve technical skills and offer opportunities to develop new surgical techniques for closure of the MMC defect and facilitate innovations to make closure of the defect at an even earlier gestational age possible.