Continuing Education Activity

Encephalocele is usually a congenital type of neural tube defect, where a sac containing brain/meninges/cerebrospinal fluid forms outside the skull due to a bone defect. On occasions, acquired encephaloceles may result from trauma, tumors, or iatrogenic injury. This activity reviews the evaluation and treatment of encephalocele and highlights the role of the interprofessional team in the care of patients with this condition.

Objectives:

• Identify the etiology of an encephalocele.
• Review the appropriate evaluation of an encephalocele.
• Outline the management options available for an encephalocele.
• Summarize interprofessional team strategies for improving care coordination and communication in patients with encephalocele and improve outcomes.

Introduction

Encephalocele is usually a congenital type of neural tube defect (NTD), where a sac containing brain/meninges/cerebrospinal fluid (CSF) forms outside the skull through a bone defect. On occasions, acquired encephaloceles may result from trauma, tumors, or iatrogenic injury. If the sac is formed by protrusion of meninges and CSF, it is appropriately called a meningocele, but it is called an encephalocele when it contains brain tissue. However, both are commonly called encephaloceles.[1]

Repair of the encephalocele is not an emergency, and only those with skin ulceration or CSF leaks need rapid surgery to avoid meningitis. Surgery can be performed as early as two months of age but is usually delayed until about four months to several years due to the small total blood volume of infants. The surgical goals are the closure of the skull defect with a watertight dural closure and the bony defect reconstruction.

Etiology

The majority of encephaloceles are congenital. Some cases are acquired secondary to tumors, trauma, or iatrogenic injury. One of the most accepted theories for the origin of a congenital encephalocele is the incomplete separation of the surface ectoderm from the neuroectoderm after the closure of the neural folds. The cranial neuropore usually closes on day 25 of embryogenesis. A problem before this day will produce an incomplete closure with a defect not covered by skin.

Genetic and environmental factors have been implicated in the development of an encephalocele.[2] TORCH infections (toxoplasma, rubella, cytomegalovirus, herpes simplex virus) have been involved in many cases.[3] Consanguineous marriages and previous NTD pregnancies have also been implicated.[3] More than 30 different syndromes have been associated with an encephalocele, including Meckel-Gruber syndrome, Walker-Warburg syndrome, Fraser syndrome, Knobloch syndrome, Roberts syndrome, morning glory syndrome, and amniotic band syndrome. The relationship between maternal use of folate and the incidence of encephalocele is still not clear.

Epidemiology

Myelomeningocele, meningocele, encephalocele, and anencephaly comprise 80% of all NTDs. Encephaloceles represent 15%-20% of all NTDs. The incidence of congenital encephaloceles is estimated at 1 in 10,000 live births.[4][5] However, the true incidence is higher because many cases result in pregnancy termination when diagnosed in utero. The incidence is still high in developing countries. The estimated worldwide prevalence of NTDs is 180 per 100,000 live births.[6] However, in Ethiopia, it is 630 cases per 100,000 children with a prevalence of 10 encephaloceles per 100,000 children.[7]

Many NTDs have sex predominance in females, but it is more pronounced for encephalocele (4.5:1).[8] Female patients are more likely to have an occipital encephalocele (1.9:1) than an anterior encephalocele.[9] Male patients are more likely to have an anterior encephalocele. However, some studies have found similar incidences for an anterior encephalocele.[10] 

Approximately 70% to 90% of encephaloceles involve the occipital area.[11][12][13] Anterior encephaloceles are seen more commonly in Asia, Africa, and Russia, with 1 case in 3,500 to 6,000 live births. However, they are much less frequent in North America and Europe (1 case in 35,000 live births).[1] In India, location predominance is variable, with some reports showing a prevalence of occipital encephaloceles of 60%, while other reports show occipital encephaloceles as low as 26%.[14][15] Neurological problems are more frequently found in posterior encephaloceles. The frequency of incidental temporal lobe/middle cranial fossa pit defects can be as high as 22.2% in a report evaluating internal auditory canal imaging examinations, with 5% forming an encephalocele.[16]

Pathophysiology

The exact mechanism for developing an encephalocele has not been identified, but several theories had been proposed. One of the most accepted theories for the origin is a problem with the separation of the surface ectoderm from the neuroectoderm after the closure of the neural folds.[17][18][19][20] When the two layers adhere, the paraxial mesoderm can not interpose between them to form an adequate skull bone and meninges.[21] Another theory proposes that they result from the amniotic band syndrome.[22][23][24][25] 

Problems with the mesoderm have also been suggested.[26] Many years ago, it was thought that encephaloceles occurred if there was an incomplete closure of the cranial neuropore. Some authors consider that an encephalocele is caused by abnormal gene signaling from the neural tube and not caused by an anomaly during primary neural tube closure.[27] The involvement of the dorsalizing bone morphogenetic protein and the ventralizing sonic hedgehog pathway has also been implicated.[28][29] 

Anterior encephalocele development occurs from abnormal development of the foramen cecum. A diverticulum of dura usually projects anteriorly between the developing nasal and frontal bones at the fonticulus frontalis/foramen cecum. Later in embryogenesis, the diverticulum regresses, and the bone closes. However, if it does not regress, the brain can herniate through the bone defect and form an encephalocele.[30][31] Sincipital encephaloceles are classified as nasofrontal, nasoethmoidal, or naso-orbital. Nasofrontal encephalocele is the most common type, seen in 46.4% of the patients. It is followed by nasoethmoidal type in 39.2% of the patients. The naso-orbital and the combined type are the least common with 14.2%.[32] 

The bone defect occurs anterior to the cribriform plate. Nasofrontal encephaloceles result from herniation through the foramen cecum and the fonticulus frontalis and projects along the nasal bridge between the nasofrontal sutures into the glabella. Nasoethmoidal encephaloceles occur when there is herniation through the foramen cecum into the prenasal space and nasal cavity under the nasal bones and above the nasal septum. Naso-orbital encephaloceles occur along the medial orbit wall at the level of the frontal process of the maxilla and the ethmoid-lacrimal bone junction.[15][17][32]

Basal encephaloceles occur through the cribriform plate, ethmoid, or sphenoid sinuses and are usually occult. Transethmoidal encephaloceles result from herniation through the cribriform plate, sphenoethmoidal result from herniation through ethmoid and sphenoid bone, transsphenoidal result from herniation through the craniopharyngeal canal, and sphenomaxillary result from herniation through the superior and inferior orbital fissure.[15]

Associated anomalies depend on the location of the encephalocele.[32] In sincipital encephalocele, corpus callosal agenesis, arachnoid cyst, hydrocephalus, and agyria-pachygyria complex are found. Occipital encephaloceles can be associated with Chiari malformation, Dandy-Walker malformations, and callosal or migrational anomalies.

History and Physical

A visible skin-covered mass near the midline in the head's anterior or posterior area is a sign that a patient has an encephalocele. The anterior encephalocele is usually related to the nasal bridge, glabella, or medial orbit. In the posterior area, it can be above or below the torcula. The sac can be mostly filled with CSF and can be translucent.

Depending on the size, the encephalocele can cause severe facial deformity and hypertelorism.[13] The patient's vision is usually good. Those involving the intranasal area can cause nasal obstruction, snoring, CSF leak, or meningitis.[33] Spasticity can occur in very large posterior encephaloceles with a large amount of brain tissue inside the sac. 

An anterior encephalocele's most common presenting symptom is nasal obstruction, followed by CSF rhinorrhea and meningitis. Less frequent presentations included hypertelorism.[10] An anterior basal encephalocele's most common location is the cribriform plate (64.0%), followed by the ethmoid roof (31.3%) and sphenoid or sella (15.5%).[10]

In posterior encephalocele, hydrocephalus is common in 40% to 60% of occipital cases.[9][34] Frontal encephaloceles have hydrocephalus in only 14% of the cases.[34] Seizures in occipital encephalocele occur in 17%,[9][34] but are uncommon in anterior cases.[34] Temporal lobe/middle cranial fossa encephaloceles can present with sudden CSF otorrhea or rhinorrhea. Repeated episodes of meningitis can occur before the diagnosis is established.

Evaluation

Prenatal ultrasound, often performed between the 9th and 11th weeks of gestation, is the mainstay imaging showing a fluid-filled sac through a skull defect.[35][36] However, by 13 weeks, it will show if the defect is a meningocele (without brain tissue herniation) or an encephalocele.[35]

DNA testing for chromosomal abnormality screening can be done at ten weeks.[35] However, patients with a screen negative cell-free DNA test result can still show abnormal ultrasound results in 3.5%.[37] It has been reported that chromosome abnormalities can be missed in 8% of the cell-free DNA screening in maternal plasma samples.[38]

Prenatal magnetic resonance imaging (MRI) will easily show the defect but will require fetal sedation. Postnatal brain MRI is the study of choice as it shows the defect, the contents, brain tissue, and any associated anomalies. A computed tomographic (CT) scan of the head with three-dimensional reconstruction is done to evaluate the skull defect, bone anomalies, and hydrocephalus. Angiography is used if the defect is close to the dural sinuses. This can be done using CT or MRI angiography.

Treatment / Management

The treatment of encephalocele is surgical. The goals are to repair the bone defect with a water-tight dural closure, eliminate the excess skin, and remove the non-functional brain tissue. When an anterior encephalocele is removed in infants or young children, the facial skeleton will remodel substantially. Craniofacial reconstruction is required for extensive frontal cases to correct hypertelorism and bone defects. 

The surgical approach is usually open, but an endoscopic approach can be used when an anterior encephalocele involves the sphenoid/ethmoid region. Endoscopic endonasal surgery for anterior basal encephaloceles provides a relatively favorable risk-benefit profile, with a low postoperative CSF leak rate.[10][39] Anterior encephaloceles recur after the endoscopic approach in 5% to 9% of patients necessitating a revision procedure.[10][40]

The time to perform surgery depends on the size, location, associated complications, and whether a skin layer covers the encephalocele. If a skin layer is present and acts as a protective cover, surgery can be delayed for a few months or years. If no layer of skin protects the encephalocele, surgery is recommended shortly after birth. Children with basal encephaloceles should have an early surgical correction to prevent infections and the progressive herniation of intracranial contents.[15] 

For sincipital or basal encephalocele surgery, the low blood reserve in small children and technical anatomic challenges must be weighed against the risks of facial deformity, airway compromise, and infection. As a result, some have recommended deferring surgery until the age of 2 to 3 years if there is no evidence of active rhinorrhea or a life-threatening condition. However, others have recommended surgery as early as two months as there is sufficient nasal expansion caused by the encephalocele, decreasing the technical difficulties.[33]

Repair of the dural defect, either primarily or using pericranium, must be done in all cases. Fibrin glue is used to reinforce the closure.[17] Closure of the bone defect is done using an autologous split calvarial bone graft, titanium mesh, and osteoconductive bone material.[15] If the defect is small, a repair is not needed. Intraoperative lumbar drainage for 5–7 days can be used to prevent CSF leaks.[15] Postoperative CSF leak develops in 6.0% of cases but responds well with lumbar drainage.[10] Reexploration for CSF leak occurs in 1% to 2% of the cases.

Differential Diagnosis

• Nasal glioma
• Cranial dermal sinus tract
• Nasal dermoid cyst
• Nasal epidermoid
• Dacryocystitis
• Dacryocystocele
• Hemangioma
• Nasal polyp

Prognosis

Many factors play a role in the prognosis of an encephalocele, like the location, the size, the amount of brain inside the sac, the presence of dural sinuses in the sac, and the presence of the hydrocephalus.[11][41] The prognosis is better for patients with frontoethmoidal encephaloceles than for patients with occipital or parietal encephaloceles. The prognosis also depends on the presence of additional congenital anomalies of the brain. A study evaluating clinical predictors showed that hydrocephalus and the presence of other intracranial abnormalities were significant predictors for the developmental delay on multivariable analysis.[4] Univariate analysis showed that seizure disorder, microcephaly, and brain tissue in the sac were significantly associated with a poor outcome.[4] Hydrocephalus is present in 34% of all patients before surgical repair of the defect, while it develops in 4% of them after the defect is closed.[9]

Long term evaluation of children with encephaloceles shows that 48% had adequate development, 11% had mild impairment, 16% had a moderate impairment, and 25% had severe impairment.[4] Occipital encephaloceles carry a worse prognosis than frontal encephaloceles due to seizures and hydrocephalus.[34] Approximately half of the patients with occipital encephaloceles are unable to live independently in society.[34] 

Factors that increase mortality include low birth weight, multiple intracranial defects, and Black race.[11] In large series, mortality has been reported between 4%-30%.[9][10][42] Approximately 76% of deaths occur on the first day of life, and roughly 71% survive to 1 year of age, and 67% to 20 years of age.[11]

Complications

The most common complications are CSF leaks and meningitis. The endoscopic approach repair complication rate of 14% compares favorably to over 20% reported in open procedures.[33]

• CSF leak
• Meningitis
• Seizures
• Hydrocephalus
• Endoscopic recurrence
• Developmental delay
• Developmental impairment

Consultations

• Neurosurgeon
• Plastic surgeon
• Craniofacial surgeon
• Otolaryngologist
• Intensivist
• Neurologist
• Endocrinologist
• Cardiologist
• Neurorehabilitation
• Geneticist

Deterrence and Patient Education

Prenatal ultrasound is usually performed between the 9th and 11th weeks of gestation and will show a fluid sac. Parental counseling takes place for orientation and possible termination of pregnancy. Genetic counseling may be of benefit for affected individuals and their families.

To prevent NTDs, folic acid fortification of food or folic acid supplementation during childbearing age is recommended. However, there is no clear association between folic acid insufficiency and encephalocele formation. Women of childbearing age should use 400 mg of folic acid daily.

Special remedial education and other medical, social, and vocational services are recommended for those children with developmental delays.

Enhancing Healthcare Team Outcomes

Patients often have complex medical and neuro disabilities, and an interprofessional team approach is essential. Coordinating care is most appropriately done within this team. Endocrine abnormalities accompany many midline malformations that can be present in encephaloceles; thus, endocrinological evaluation is necessary. Morbidity and mortality have greatly improved with the use of brain MRI, better neurosurgical techniques, and a dedicated neonatal intensive care. The neuroradiologist provides the interpretation of studies to determine the cause of the defect and associated anomalies. Additional studies needed can be recommended before surgery.

While a primary clinician is almost always involved in the care of patients with an encephalocele, it is important to consult with an interprofessional team of specialists that includes an obstetrician, neurosurgeon, neurologist, intensivist, craniofacial specialist, and plastic surgeon. The integrated care pathway, combined with an evidence-based approach, will provide the patient's best outcomes.