A Term Infant With a Fetal Brain Anomaly

Newborn full-term female with a soft, unruptured posterior cranial mass.Born to a 36-year-old gravida 5, now para 5 womanPrenatal course significant for late prenatal care in mid-third trimester, low-risk noninvasive prenatal testing, advanced maternal age, polyhydramnios, and first prenatal ultrasonography at 37 weeks’ gestation notable for meninges and brain matter protruding from the posterior craniumMaternal medications: prenatal vitaminsEstimated gestational age: 38 weeks and 6 daysScheduled cesarean section to decrease risk of rupture of the brain lesionMaternal serologies negative, except for unknown Group B Streptococcus, treated adequatelyBorn vigorous with good tone, allowing delayed cord clamping; uncomplicated resuscitation with Apgar scores 8 and 9 at 1 and 5 minutes, respectivelyIn the delivery room, the female infant was noted to have a large posterior cranial mass that was unruptured, covered by a soft, thin membrane, measuring 6 cm × 6 cm × 6 cm (Figure 1). Soon after birth, the mass was wrapped in moist gauze and the infant was placed prone for transport to the neonatal intensive care unit (NICU), where she was admitted for stabilization and surgical planning.Heart rate: 120 beats per minuteRespiratory rate: 47 breaths per minuteBlood pressure: 67/31 mm Hg, cuffOxygen saturation: 98% (in room air)Temperature: 98.6 °F (37 °C)Measurements: birthweight 3450 g (70th percentile); length 50 cm (65th percentile)General appearance: well-appearing infant sleeping in no distressHead: large mass present over posterior occiput, with vessels visible through overlying membrane; nonruptured; anterior fontanelle open, soft, flat; microcephalyFace: eyes normally shaped and spaced; low-set ears without pits or tags bilaterally; intact palate with high archLungs: no distress, clear to auscultation bilaterallyCardiovascular: normal sinus rhythm, no murmurs, well perfusedAbdomen: Soft, nontender, nondistended, no organomegaly, bowel sounds present; 3-vessel cordGenitourinary: normal external female genitalia; anus patentSpine: straight, sacral dimple with base visualized above the gluteal cleftExtremities: no polydactylySkin: pink with mild peelingNeurological: grasp, suck, and Moro reflexes intact; moving all extremities spontaneously; decreased tone in upper extremities bilaterally; appropriately reactive to exam.White blood cell count: 11.3 × 103/μL (11.3 × 109/L) with 44% neutrophils, 36% lymphocytesHemoglobin: 18.1 g/dL (181 g/L)Platelet count: 268 × 103/μL (268 × 109/L)Capillary blood gas: pH 7.29, pCO2 50 mm Hg (6.7 kPa), base deficit 3.4 mEq/L (−3.4 mmol/L)On admission, the infant was started on maintenance intravenous fluids. Karyotype and microarray were drawn. That same day, after an echocardiogram and abdominal ultrasonography demonstrated normal anatomy, the patient started oral ad lib feeding with expressed breast milk. One day after birth, brain magnetic resonance imaging (MRI) showed a large occipital encephalocele containing the posterior inferior cerebellum, occipital lobes, and superior sagittal sinuses; these findings were consistent with Chiari Type III malformation (CMIII) (Figure 2). The degree of brain stem involvement in conjunction with the course of the dural venous sinuses into the encephalocele (Figure 3)—particularly the inferior sagittal sinus and the straight sinus—placed the patient at high risk for severe hemorrhage or poor outcome, precluding operative intervention by neurosurgery. The infant subsequently resumed oral feedings but required some gavage feedings due to sleepiness. After evaluation by a feeding specialist, the infant transitioned to full gavage feedings at 7 days of age.A multidisciplinary family meeting was held with the palliative care, neurosurgery, and neonatology teams at 5 days of age. The clinicians reviewed the infant’s images with the family, discussed the potentially poor prognosis, and recommended supportive care. In the setting of the infant’s high-arched palate, low-set ears, hypotonia with CMIII, and normal karyotype [46, XX] and microarray, further genetic evaluation was also recommended.1 Whole-exome sequencing was offered, but the family declined. After the meeting, the parents requested a second opinion.Encephalocele with possible unidentified genetic conditionMeckel-Gruber syndromeFraser syndromeJoubert syndromeKnobloch syndromeEncephalocele with possibly unidentified genetic conditionOn arrival at a second quaternary NICU at 19 days of age, the patient was stable on full gavage feedings. MRI was repeated, demonstrating interval enlargement of the occipital encephalocele, measuring 8.8 cm × 6.8 cm × 7.7 cm, likely due to accumulating fluid from the entrapped occipital horns (Figures 4 and 5). MR venography and MR angiography studies confirmed that portions of the posterior inferior superior sagittal sinus and straight sinus were inside the encephalocele sac, along with a significant amount of brain tissue, measuring approximately 1.9 cm × 1.9 cm × 1.9 cm.At 22 days of age, a multidisciplinary family meeting was held with neurosurgery, neurology, and neonatology. The team discussed that while the extent of the malformation was concerning for a high likelihood of severe neurodevelopmental delays, it did not preclude surgical options. The team discussed goals of care, and, after thoughtful deliberation, the family decided to proceed with surgery.After careful size assessment (Figure 6) and sonographic evaluation of venous sinus/vasculature involvement (Figure 7), the patient underwent left frontal ventriculoperitoneal shunt placement at 26 days of age, followed by encephalocele resection at 33 days of age (Figure 8).One day after resection, MRI showed decreased ventricular size, a small residual occipital encephalocele still containing portions of the bilateral occipital lobes and cerebellar hemispheres, and a small medial right occipital lobe hemorrhage (Figure 9). Serial MRIs on postoperative days 4 and 10 were improved (Figures 10 and 11). Clinically, the patient was improving as well; by postoperative day 5, she was extubated, weaned off sedation, and tolerated enteral nasogastric feedings. The intermittent bradycardia, oxygen desaturations, and hypertension events of the first postoperative week eventually resolved, with no signs of sepsis or seizures. Although her oral feedings improved postoperatively, she ultimately required gastrostomy tube placement to support enteral nutrition. The patient’s postnatal oral feeding challenges and antenatal polyhydramnios, potentially from abnormal in-utero swallowing, are both indicative of neurologic impairment associated with the encephalocele. The infant was discharged home at 61 days of age with neurosurgery, neurology, pediatric surgery, cardiology, ophthalmology, audiology, and high-risk infant clinic follow-up, as well as outpatient physical and occupational therapies. Cholecalciferol was her only prescribed home medication.CMIII is defined by occipital and/or cervical defects with neural tissue herniation2,3; cerebellar involvement within the encephalocele is considered an additional diagnostic criterion.2,4,5 Although it is thought of as a neural tube defect, CMIII has an unclear pathogenesis.6 Theories include improper extension of the ventricles leading to failure of neural tube closure, which causes persistent cerebrospinal fluid (CSF) leakage and results in an occipitocervical defect.2 The lack of ventricular distension during development causes neural and calvarial underdevelopment, leading to small or absent posterior fossa, allowing occipital, cerebellar, and/or brain stem herniation.7Prognosis in neonates with CMIII has evolved from incompatible with life to dismal after repair, to variable, depending on the amount of neurologic tissue involved in the encephalocele and the infant’s clinical status.2,8 MRI and MR venography studies have become standard for diagnosing encephaloceles and delineating the exact anatomical abnormalities. In particular, identifying venous sinuses is important for avoiding massive bleeding if operative intervention is pursued. Neurodevelopment can vary from appropriate to severe delays.2 Patients often require multispecialty care.Factors affecting the decision for surgical repair include the neurological and respiratory status as well as technical considerations such as size of encephalocele, closed or ruptured sac, involvement of venous sinuses/vasculature, and amount of neurologic tissue contained inside.4,9 The main aim of treatment is to close the dura in a water-tight manner while minimizing the chances of hydrocephalus in the future.2,8–10 For this reason, the surgical plan is stepwise, first with CSF diversion via a ventriculoperitoneal shunt, followed by encephalocele repair/reduction. Often, partial amputation of the herniated tissue is necessary for proper closure.2 Serial MRIs are performed following repair to monitor for postoperative stroke, hemorrhage, and/or CSF leak.CMIII can be associated with several genetic conditions. In the setting of other atypical findings, this infant is likely to have an associated genetic syndrome; however, the infant’s specific findings do not fit a known genetic disorder. Genetic possibilities include Meckel-Gruber syndrome, Fraser syndrome, and Joubert syndrome. Although infants with Meckel-Gruber syndrome have microcephaly and cleft lip/palate, affected patients also typically have microphthalmia, polydactyly, polycystic kidneys, and/or ambiguous genitalia, which were not found in this patient. Fraser syndrome involves craniofacial abnormalities, laryngeal malformations, syndactyly, and genitourinary anomalies, which were not seen in this patient. Orofacial clefting and hypotonia are consistent with Joubert syndrome; however, the associated polydactyly and renal and hepatic abnormalities were also not found in this patient. The less-common Knobloch syndrome is found in patients with CMIII and involves tectocerebellar dysraphism; these skull and vision defects result in tachypnea, opsoclonus, and ataxia due to cerebellar hypoplasia with tectal plate deformity but do not fit with this patient’s findings.1SummaryImportant aspects of physical examination in infants who present with encephalocele are size, relative location, and presence/absence of CSF leak; protecting the neural tissue with a moist covering and prone or lateral positioning to off-load pressure is important for patients with an exposed encephalocele.Infants born with CMIII have variable prognoses depending on specific encephalocele characteristics, the infant’s clinical status, and if an underlying genetic condition is present. Depending on the family’s goals of care and the feasibility of surgery, clinically appropriate services beyond palliative care can be offered.Encephalocele repair often requires 2 surgeries: ventriculoperitoneal shunt placement and encephalocele repair/resection. Hydrocephalus is a common complication of CMIII both pre- and postoperatively.American Board of Pediatrics Neonatal-Perinatal Content SpecificationKnow various neural tube development disorders and surgical and complex NICU patient management.Understand perioperative care of newborn infants (eg, respiratory, fluid, temperature, antibiotics, pain management).