Double Myelomeningocele Repair by Fetal Surgery with a Single Micro-Hysterotomy

Abstract Introduction: Open spina bifida (OSB) is the most common congenital anomaly of the central nervous system. It is associated with severe neurodevelopmental delay, motor impairment, hydrocephalus, and bowel and bladder dysfunction. In selected cases, intrauterine spina bifida repair has been shown to improve neonatal outcomes. Rarely, the spine can have a double defect compromising two different segments and there is a lack of evidence on the feasibility and benefits of intrauterine repair in these cases. Case Presentation: We present a case with both cervicothoracic and lumbosacral myelomeningocele, Arnold-Chiari malformation type II and bilateral ventriculomegaly, that was treated successfully at 25 weeks with open micro-neurosurgery. Double myelomeningocele was successfully treated through a single 2-cm micro-hysterotomy, by performing external versions to sequentially expose and repair both defects. Weekly postoperative follow-up showed no progression of ventriculomegaly or complications attributable to the procedure. Preterm rupture of membranes prompted a conventional cesarean delivery at 32 weeks of gestation. Neurodevelopmental outcome at 20 months was within normal ranges, having achieved ambulation without orthopedic support and with no need for ventriculoperitoneal shunting. Conclusion: This report demonstrates for the first time the feasibility of double OSB repair through a single 2-cm micro-hysterotomy, suggesting that selected isolated cases of double myelomeningocele could be candidates for fetal intervention. Further prospective studies should be carried out to assess the potential benefit of double OSB intrauterine open repair. Established Facts Prenatal surgery has been established as the ideal treatment for open spina bifida based on the MOMS trial, which showed a reduction in the need for ventriculoperitoneal shunt placement and better postnatal neurological and motor function. Double myelomeningocele is very rare with only a few cases reported in the literature.

In selected cases, intrauterine spina bifida repair has been shown to improve neonatal outcomes.Rarely, the spine can have a double defect compromising two different segments and there is a lack of evidence on the feasibility and benefits of intrauterine repair in these cases.Case Presentation: We present a case with both cervicothoracic and lumbosacral myelomeningocele, Arnold-Chiari malformation type II and bilateral ventriculomegaly, that was treated successfully at 25 weeks with open micro-neurosurgery.Double myelomeningocele was successfully treated through a single 2-cm micro-hysterotomy, by performing external versions to sequentially expose and repair both defects.Weekly postoperative follow-up showed no progression of ventriculomegaly or complications attributable to the procedure.Preterm rupture of membranes prompted a conventional cesarean delivery at 32 weeks of gestation.Neurodevelopmental outcome at 20 months was within normal ranges, having achieved ambulation without orthopedic support and with no need for ventriculoperitoneal shunting.Conclusion: This report demonstrates for the first time the feasibility of double OSB repair through a single 2-cm micro-hysterotomy, suggesting that selected isolated cases of double myelomeningocele could be candidates for fetal intervention.Further prospective studies should be carried out to assess the potential benefit of double OSB intrauterine open repair.

Case Report
A 32-year-old pregnant woman, gravida 1, was referred to our fetal surgery center at 23+3 weeks+days of gestation due to a neural tube defect.Fetal neurosonography showed scalloping of frontal bones (lemon sign), obliteration of cisterna magna with posterocaudal displacement of cerebellar vermis (Arnold-Chiari malformation type II), bilateral ventriculomegaly (Fig. 1).Evaluation of the fetal spine demonstrated a superior neural tube defect from C4 to T1 and an inferior neural tube defect from L3 to S1 (Fig. 2), with adequate mobility of the lower limbs showing ankle plantar flexion (functional level S1).Fetal Doppler evaluation of the umbilical artery, middle cerebral artery, and ductus venosus was normal, and the cervical length was 36 mm.Amniocentesis for karyotyping was performed, reporting a normal female (46, XX).The patient was reassessed at 25 weeks of gestation and presented a progression of ventriculomegaly (mean lateral ventricle diameter of 12 mm) with preserved lower limb mobility.
The parents were counseled regarding the potential risks and benefits of prenatal surgery versus expectant management with postnatal repair.In particular, they were informed that extrapolating the existing evidence from single open spina bifida (OSB) in utero repair would suggest that potential preservation of motor function and reduction of the risk of progression of ventriculomegaly could be expected, but they were aware of the lack of evidence supporting this for double OSB repair.Termination of pregnancy was not an option due to the existing legal impediments in Mexico.
The preoperative protocol included advanced neurosonography, echocardiography, maternal psychological evaluation, and fetal magnetic resonance imaging that confirmed double myelomeningocele with cord tethering (Fig. 3).OSB repair was performed at 25 weeks of gestation by micro-neurosurgery as previously reported [1].Briefly, under maternal general anesthesia, a maternal laparotomy through a low transverse abdominal incision (Pfannenstiel) was performed to allow uterine exteriorization from the abdominal cavity.Due to anterior position of the placenta, the uterus was tilted anteriorly to expose the posterior wall.The fetus was in a podalic presentation, and therefore, gentle external manipulation was applied until the cervical defect was positioned on the midline against the posterior uterine wall away from the placenta.Under ultrasound guidance, 1-0 absorbable monofilament (Vicryl) was used to fix the uterine membranes by performing 2 trans-myometrial stitches on the midline of the uterine fundus, 2.0 cm away from each other, and following its longitudinal axis.A single 2.0-cm hysterotomy was performed between the sutures with a monopolar cautery pencil.The amniotic membranes were gently opened and fixed to the uterine wall by continuous locking suture, going over the uterine incision circumferentially, with polyglactin 1-0 thread (Ethicon Inc).A self-retaining retractor (Weitlaner) was used to maintain a good surgical window through the hysterotomy for better exposing the fetal defect.An 8Fr feeding tube was introduced into the amniotic cavity through the hysterotomy for continuous infusion of warm (37°C) lactated Ringer's solution with antibiotic (2 g cefotaxime per L) to maintain the intrauterine amniotic fluid volume throughout the surgery.Single monofilament 4-0 stitches involving healthy fetal skin were placed on each side of the spinal defect, and the threads were exteriorized through the hysterotomy, allowing a gentle pulling of the fetus against the uterine wall to aid in exposing the defect through the surgical window and reduce amniotic fluid leakage (fetal fixation).Due to the small hysterotomy diameter, surgical loupes (×4.5) were used by the pediatric neurosurgeon (FCO) to improve illumination, magnification, and visualization of the neural placode, which was released and positioned within the spinal canal, and then a 3-layer watertight closure of the neural defect was performed using a monofilament 4-0 suture with a 17-mm needle and bipolar cautery (Fig. 4).The cervical defect was first repaired, and then, after removing fetal fixation stitches, the micro-hysterotomy edges were temporarily affronted using 2 Allis forceps.This was to maintain adequate amniotic fluid volume for the ultrasound guidance to perform an external version to cephalic presentation and expose the lumbosacral defect through the same hysterotomy.The fetus was fixed for a second time exposing the lumbar region, and surgical repair was repeated as previously described.The size of both neural tube defects was larger than the hysterotomy, and therefore, dissection and suturing were accomplished by traversing the lesions with a gentle mobilization of the uterine retractor while holding the fetal back against the hysterotomy.During the entire procedure, continuous fetal monitoring was performed by a fetal cardiologist by using fetal Doppler ultrasound.Once the pediatric neurosurgeon completed both myeloplasties, the fetal surgeon performed a 2-layered uterine closure.The uterus was then placed back into the abdominal cavity, and the maternal abdominal wall was closed in 3 layers.The surgical time was 150 min, and no intraoperative complications (chorioamniotic separation, rupture of membranes, placental abruption, massive uterine bleeding requiring maternal blood transfusion, or fetal bradycardia) were reported.Prophylactic tocolysis with indomethacin and nifedipine was administered immediately after wound closure and up to 72 h after the procedure.The patient was discharged 1 week after fetal surgery.A weekly follow-up showed normal amniotic fluid, fetal estimated weight within normal ranges, and normal cervical length.During fetal follow-up, fetal neurosonography showed regression of hindbrain herniation (the obliterated cisterna magna became visible and measurable, and the cerebellar fastigium regressed to a normal morphology and position above the foramen magnum) and mild progression of ventriculomegaly (mean lateral ventricle diameter of 14 mm).
At 32 weeks of gestation, preterm rupture of membranes prompted an emergency cesarean delivery 72 h after a course of corticosteroids (betamethasone, 12 mg, 2 doses, 24 h apart) was administered.The neonate had respiratory distress syndrome and required oxygen support for 1 week.Physical examination revealed normal head circumference and two surgical scars, one in the lower cervical region and the other in the upper lumbar region.There was no cerebrospinal fluid (CSF) leak.A computed  Prenatal Repair of Double Myelomeningocele tomography scan was performed 4 months after birth and reported a supratentorial dilated ventricular system without hydrocephalus nor Chiari II malformation (Fig. 5), and therefore, there was no need for ventriculoperitoneal shunting.
Neurodevelopmental outcome was assessed at 24 months by using Bayley Scales of Infant Development, third edition (BSID-III).Neurodevelopment was within normal ranges with BSID-III psychomotor and mental development index score of ≥70, having achieved ambulation without orthopedic support (Fig. 6).

Discussion
OSB is the most common congenital anomaly of the central nervous system due to a failure of primary neurulation.The dysraphic spinal cord protrudes through the vertebral defect and is exposed to the chemically hostile environment of the amniotic fluid and susceptible to trauma against the uterine wall.There is also CSF leakage to the amniotic cavity, interfering with its normal circulation and leading to hydrocephalus that may require postnatal ventriculoperitoneal shunting.The lifelong consequences include motor and neurodevelopmental impairment, skeletal deformation, and bowel, bladder, and sexual dysfunction [2].A randomized control trial "Management of Myelomeningocele Study" (MOMS) demonstrated that prenatal surgery improves prognosis [3].In comparison with postnatal surgery, intrauterine spina bifida repair has shown a significant reduction in the need for postnatal ventriculoperitoneal shunt placement and better neurological and motor function [3][4][5].Therefore, the number of centers offering this fetal intervention for selected cases with isolated OSB is growing worldwide [6,7].Double neural tube defects on the spine are rare, accounting for less than 1% of all defects [8], and are considered a severe condition associated with hydrocephalus often requiring postnatal ventriculoperitoneal shunting, severe motor and neurological impairment, and even infant death [9][10][11][12][13][14][15].There are only a few cases of double neural tube defects reported in the literature, with a very small proportion of them having been diagnosed prenatally [15,16], and all of them receiving postnatal surgical repair [17][18][19].Thus, there is a lack of previous evidence on fetal surgery for this specific population.We are therefore reporting for the first time a case of double myelomeningocele that was successfully repaired during fetal life by open fetal microneurosurgery using a single 2.0-cm micro-hysterotomy.
This surgical technique has recently been described by our group in a prospective cohort of 60 consecutive cases with isolated OSB [1].We demonstrated that intrauterine spina bifida repair through a 1.5-2.0-cmmicro-hysterotomy was feasible and showed better perinatal outcomes and similar short-term neurological outcomes than the classic open fetal surgery technique.Maintaining normal amniotic fluid and uterine volume by continuous amnioinfusion and minimizing amniotic fluid leak and fetal manipulation by fetal fixation sutures are keys to the procedure [20].This technique has been shown to be associated with lower risk of oligohydramnios, preterm rupture of the membranes, and preterm delivery than the standard open technique using 6-8-cm hysterotomy [21,22].In the current case, double spina bifida repair was feasible by a single microhysterotomy by performing an internal version for exposing the second defect while the hysterotomy was temporally occluded.Considering that umbilical cord prolapse is a potentially lethal complication that may occur during open fetal surgery [23], the relevance of a small hysterotomy and affronting its edges during internal version should be remarked, since these avoid rapid loss of amniotic fluid and possible umbilical cord prolapse during fetal manipulation.Compared to postnatal treatment, prenatal surgery for single myelomeningocele has been shown to reduce hindbrain herniation and the need for CSF shunting, improve motor function, and increase the probability of independent ambulation [24,25].Alike to single myelomeningocele repair, in this case, intrauterine double OSB repair resulted in regression of Chiari II malformation, avoiding the need of ventriculoperitoneal shunting, and allowing good neurodevelopmental and motor outcomes.Nevertheless, in the current case, fetal intervention was mainly indicated by the lumbosacral defect since cervical spinal defects are usually not associated with hydrocephalous or motor dysfunction, and therefore, further prospective and multicenter studies are required to confirm the potential benefit of this intervention in cases with isolated multiple neural tube defects.
Of note, no complications were observed during or after surgery in our case, but we recognize that this surgical procedure is not risk-free and has been associated with fetal complications such as placental abruption, bradycardia, and intrauterine fetal demise.Although no maternal deaths have been reported, severe life-threatening maternal complications such as severe uterine bleeding, uterine rupture, pulmonary edema/embolism, and even cardiac arrest requiring resuscitation have also been reported [1,26,27].
In our previous series of 60 cases with single spina bifida treated with intrauterine repair by micro-hysterotomy, the surgery time was on average 107 min (SD 30 min) [1].Although double myeloplasty implied longer neurosurgical time (150 min), it could be speculated that maternal or fetal risks are not increased during prenatal surgery for double defects in comparison with single defects, since this was a single-stage surgery using only one micro-hysterotomy.
We recognize that double spina bifida is unusual and its prenatal diagnosis may be very challenging [10].Some series have demonstrated that in a proportion of cases, only one of the defects was observed during pregnancy while the second defect was only diagnosed after birth [17].Therefore, once an OSB is diagnosed in pregnancy, a  Prenatal Repair of Double Myelomeningocele thorough ultrasound examination of the entire fetal spine should be performed to look for a second hidden defect.In conclusion, simultaneous intrauterine repair of double spina bifida through a single 2-cm micro-hysterotomy in a single-stage surgery is feasible and therefore selected cases of isolated double myelomeningocele with Chiari II malformation should not be excluded for the potential benefits of fetal intervention.

Fig. 2 .
Fig. 2. Fetal sonographic imaging of the double myelomeningocele.Sagittal view of the cervical (a) and lumbosacral (d) region of the fetal spine showing a myelomeningocele.Coronal view shows the splayed vertebrae as the result of the spinal defect in the cervical (b) and lumbosacral (e) regions.Ultrasound 3D reconstruction of the fetal spina shows both splayed vertebrae, in the cervical region (arrow on top) and the lumbosacral region (second arrow) (c).

Fig. 3 .
Fig. 3. Sagittal slice of fetal magnetic resonance imaging (MRI) T2weighted sequence demonstrating Arnold-Chiari II malformation.Hindbrain herniation is caused by a downward displacement of the cerebellum resulting in a compressed brainstem, small posterior fossa, and obstructed fourth ventricle.Double myelomeningocele is shown, at cervical region and at lumbosacral region with cord tethering.

Fig. 5 .
Fig. 5. Computed tomography scan at 4 months of age after intrauterine myelomeningocele repair.a Axial slice shows no hydrocephalus.b Sagittal slice shows no tonsillar herniation.

Fig. 4 .
Fig. 4. Intraoperative image of open myelomeningocele defect repair.Stapled micro-hysterotomy (2 cm) shows the edge of the myometrium and chorioamniotic membranes fixed with surgical suture (a), tubulation of the neural placode (b), and closure of dura mater (c) and fetal skin (d).Temperature irrigation tube (blue tube) is inserted into the uterus to maintain the uterine volume.