Encephalocele

Etiology

Most encephaloceles are congenital, with a smaller proportion acquired due to trauma, tumors, or iatrogenic injury. A widely accepted theory for developing congenital encephaloceles involves the incomplete separation of the surface ectoderm from the neuroectoderm during neural fold closure.[4] This process typically occurs between days 25 and 27 of embryogenesis—defects arising before this closure may result in a lesion not covered by skin.

Both genetic and environmental factors contribute to the development of encephaloceles.[5] Toxoplasma, Rubivirus rubellae, cytomegalovirus, and human herpesvirus-1 and -2 infections have been implicated in several cases.[6] Additional risk factors for a pregnancy affected by encephalocele include consanguinity and a previous history of one or more pregnancies with a neural tube defect (NTD).[6] Over 30 syndromes are associated with encephaloceles, including Meckel-Gruber, Walker-Warburg, Fraser, Knobloch, Roberts, morning glory, and amniotic band syndromes.[7][8] While maternal folate supplementation has reduced the incidence of many NTDs, its specific relationship with encephaloceles remains unclear.

Epidemiology

Myelomeningocele, meningocele, encephalocele, and anencephaly account for 80% of all NTDs; encephaloceles comprise 15% to 20% of these lesions. The incidence of congenital encephalocele is estimated at 1 in 10,000 live births, though the true incidence may be higher due to pregnancy terminations following prenatal diagnosis.[9][10] The incidence is particularly elevated in low-resource countries, with Ethiopia reporting 630 NTD cases per 100,000 children and a prevalence of 10 encephaloceles per 100,000 children.[11] Globally, NTDs have a prevalence of 180 per 100,000 live births.[12]

While males and females are equally affected overall, specific patterns emerge for certain encephalocele types. Occipital encephaloceles are more common in females, with studies showing a female-to-male ratio of 1.9:1.[13] Conversely, anterior cranial fossa encephaloceles show a slightly higher incidence in males, with a ratio of 1.1:1.[14] Approximately 70% to 90% of encephaloceles occur in the occipital region, particularly in North America and Western Europe.[15][16][17] Anterior skull base encephaloceles are more prevalent in Asia, Africa, and Russia, with 1 case in 3500 to 6000 live births. However, these particular defects are much less frequent in North America and Europe (1 case in 35,000 live births).[3] 

Incidental findings of temporal lobe/middle cranial fossa defects are frequent, with 22.2% reported in internal auditory canal imaging and 5% forming encephaloceles.[18] Regional variations in location predominance have been reported, such as variable occipital encephalocele prevalence in India, ranging from 26% to 60%.[19][20]

Pathophysiology

The precise mechanism underlying encephalocele development remains unidentified, but several theories have been proposed. A widely accepted theory suggests that encephaloceles result from defective separation of the surface ectoderm from the neuroectoderm following neural fold closure, often considered a "late" neurulation defect during the fourth week of gestation.[21][22][23][24][25] When these layers remain adherent, the paraxial mesoderm cannot interpose effectively to form a robust skull and meninges.[26] Sincipital and basal encephaloceles are theorized to stem from abnormal prosencephalic neural crest development, leaving midline foramina patent.[27] Another theory links encephaloceles to amniotic band syndrome.[28][29][30][31]

Defects involving the mesoderm have also been implicated, and earlier beliefs attributed encephaloceles to incomplete cranial neuropore closure.[8][32] Recent perspectives suggest abnormal gene signaling from the neural tube, rather than anomalies during primary neural tube closure, may play a role.[33] Genetic pathways such as the Sonic Hedgehog (SHh) pathway, Wnt signaling, and glioma-associated oncogene transcription factors have been implicated, highlighting the potential influence of genetic and molecular factors in encephalocele pathogenesis.[34]

Anterior skull base encephaloceles arise due to abnormal development of the foramen cecum. During embryogenesis, a diverticulum of the dura projects anteriorly between the developing nasal and frontal bones at the fonticulus frontalis/foramen cecum. This diverticulum typically regresses, allowing the bone to close. Failure of regression results in brain herniation through the bony defect, forming an encephalocele.[35][36]

Sincipital encephaloceles are categorized as nasofrontal, nasoethmoidal, or nasoorbital. In a retrospective review, nasofrontal encephaloceles were the most common (46.4%), followed by nasoethmoidal (39.2%), with nasoorbital and combined types being the least frequent (14.2%).[37] Nasofrontal encephaloceles project along the nasal bridge through the foramen cecum and fonticulus frontalis into the glabella. Nasoethmoidal encephaloceles herniate into the prenasal space and nasal cavity beneath the nasal bones and above the nasal septum. Nasoorbital encephaloceles extend along the medial orbital wall at the frontal process of the maxilla and the ethmoid-lacrimal junction.[20][21][37]

Basal encephaloceles occur through the cribriform plate, ethmoid, or sphenoid sinuses and are typically occult. Specific subtypes include transethmoidal encephaloceles, which herniate through the cribriform plate; sphenoethmoidal encephaloceles, which herniate between the ethmoid and sphenoid bones; transsphenoidal encephaloceles, which herniate through the craniopharyngeal canal; and sphenoorbital encephaloceles, which herniate through the superior and inferior orbital fissures.[20]

Associated anomalies vary by encephalocele location.[37] Sincipital encephaloceles are often linked to corpus callosal agenesis, arachnoid cysts, hydrocephalus, and agyria-pachygyria complex. Occipital encephaloceles may co-occur with Chiari malformations, Dandy-Walker malformations, and callosal or migrational anomalies. These associations underscore the importance of thorough evaluation in affected patients.

History and Physical

Medical History 

The clinical presentation of an encephalocele is dictated by its location, size, and content. Many congenital encephaloceles are identified prenatally on ultrasonography or during infancy due to visible cranial protrusions. A family history of NTDs or consanguinity may be noted, as well as maternal exposure to teratogens or infections such as ToRCHeS pathogens. Prenatal imaging often reveals cranial abnormalities, prompting further investigation. In contrast, acquired encephaloceles typically arise after head trauma, cranial surgery, or in the presence of intracranial tumors. Patients with acquired lesions may present with symptoms of raised intracranial pressure or neurological deficits following the precipitating event.

Physical Examination

In patients with a congenital encephalocele, a visible skin-covered mass near the midline is often visualized during prenatal ultrasonography and will be evident after birth if not discovered prenatally. Anterior encephaloceles are usually related to the nasal bridge, glabella, or medial orbit. Compared to nasal gliomas, the sac can be mostly filled with CSF and translucent (see Image. Nasal Encephalocele). Additionally, the sac of an encephalocele is often more compressible than that of a nasal glioma. Depending on the size, the encephalocele can cause severe facial deformity and hypertelorism.[17] The patient's vision is usually preserved depending on the extent of herniation. Encephaloceles involving the intranasal area can cause nasal obstruction, snoring, CSF leaks, or meningitis.[38] Spasticity can occur with very large posterior encephaloceles that contain a large amount of brain tissue inside the sac. 

Sincipital encephaloceles may not be grossly evident after birth but may present with hypertelorism, orbital dystopia, and telecanthus, among other craniofacial deformities.[34] Basal encephaloceles can present with a nasal or epipharyngeal mass, recurrent infections, and meningitis secondary to CSF leaks.[39] Depending on the contents of the herniation, some transsphenoidal encephaloceles can contain the pituitary gland and the optic apparatus, leading to endocrinopathies and visual disturbances.[40]

With parietal and occipital encephaloceles, concurrent hydrocephalus is common, occurring in 40% to 60% of occipital lesions and 14% of frontal encephaloceles.[13][41] In a retrospective review of 77 children with encephaloceles, the presence of neural tissue, cranial anomalies, encephalocele size of 2 cm, seizure disorder, and microcephaly were associated with hydrocephalus on univariate analysis. However, on multivariate analysis, only the presence of neural tissue was borderline significant for associated hydrocephalus.[42] Similarly, another review of 102 cases of encephaloceles found the presence of other associated anomalies, larger encephalocele sacs, and infections were independent predictors of hydrocephalus.[43] Protzenko et al found an increased prevalence of hydrocephalus in encephaloceles that were supratorcular, especially when associated with Dandy-Walker syndrome, Chiari III malformation, and preexisting ventriculomegaly.[44] 

Seizures occur in 17% of patients with occipital encephalocele but are uncommon in sincipital and basal encephaloceles.[13][41] Temporal lobe/middle cranial fossa encephaloceles can present with sudden CSF otorrhea or rhinorrhea. Temporal encephaloceles, while often asymptomatic, have been associated with medically refractory epilepsy and found in 2% to 12% of patients undergoing workup for epilepsy.[45][46][47] In a retrospective review of 11 children with medically refractory epilepsy secondary to temporal encephaloceles, a body mass index greater than 85% for age was found in 36% of the children.[48] Similarly, Sandhu et al found that 80% of patients who underwent resection of their temporal encephalocele were overweight, highlighting the association between idiopathic intracranial hypertension and the development of temporal encephaloceles.[49]

Atretic encephaloceles are usually small, skin-covered lesions that do not have the typical CSF-filled sac of other encephaloceles. Atretic lesions are often referred to as “rudimentary” encephaloceles or meningocele manqué. Since these defects are usually not as large as many encephaloceles, the presentation may be delayed until childhood when patients present with a soft tissue mass.[50]

Evaluation

Evaluating an encephalocele involves a combination of laboratory, radiographic, and other studies to confirm the diagnosis, assess associated anomalies, and plan surgical management.

Laboratory Studies

Genetic testing: DNA testing for chromosomal abnormalities can be performed as early as 10 weeks gestation.[51] However, 3.5% of patients with a negative screening test may have abnormal ultrasonography findings.[52] Reports reveal that chromosomal abnormalities can be missed in 8% of cell-free DNA screening of maternal plasma samples.[53] 

Serum testing: When combined with ultrasonography findings, elevated biomarkers like alpha-fetoprotein in maternal serum or amniotic fluid can suggest anencephaly or encephalocele. Testing for ToRCHeS infections may also be performed if there is a suspicion of maternal exposure.

Imaging Studies

Ultrasonography: This modality is a key imaging tool, especially in prenatal diagnosis, for visualizing the defect and assessing the size and content of the sac. Prenatal ultrasonography, often performed between the ninth and eleventh gestational week, may reveal a fluid-filled sac protruding through the skull defect.[51][54] Around 13 weeks, ultrasonography can often differentiate between a meningocele and encephalocele.[51] 

Computed tomography: This imaging modality can provide detailed imaging of the skull and brain, which is particularly useful for defining the size and content of the encephalocele, as well as associated bony defects or hydrocephalus. Computed tomography (CT) can also help in planning surgical repair by identifying the extent of the encephalocele. A head CT with 3-dimensional reconstruction can be performed to evaluate the skull defect and other bone anomalies. CT angiography is used if the defect is near the dural sinuses or if there is concern for any vascular involvement. 

Magnetic resonance imaging: This imaging modality offers superior soft tissue contrast and can delineate the relationship of brain tissue with the sac, assess intracranial pathology, and provide additional details on associated brain malformations, such as hydrocephalus or Chiari malformations. Prenatal magnetic resonance imaging (MRI) can be performed prenatally and is useful for prenatal counseling. Depending on the amount of herniated brain, MRI can predict neurological outcomes.

In the postnatal period, MRI of the brain with or without angiography as dictated by the clinical picture, is the preferred imaging modality in patients with encephalocele due to superior visualization of the defect, the contents of of the sac, and any associated anomalies.

Other Studies

CSF analysis: Examining CSF via lumbar puncture or direct aspiration can help identify infections such as meningitis that may arise from a CSF leak secondary to an encephalocele.

Electroencephalogram: In cases where encephaloceles contain brain tissue, an electroencephalogram can be employed to assess for concurrent epilepsy or other electrical abnormalities.

Endoscopy: In nasoorbital or basal encephaloceles, endoscopic evaluation of the nasal cavity or paranasal sinuses can assess the anatomy and plan surgical management.

Treatment / Management

The treatment of encephaloceles is surgical, with goals that include repairing the bony defect, achieving a water-tight dural closure, eliminating excess skin, and removing nonfunctional brain tissue. In cases of anterior encephaloceles resected during infancy or early childhood, substantial remodeling of the facial skeleton can occur naturally over time. However, craniofacial reconstruction may be required to restore function and aesthetics for extensive cases involving significant craniofacial deformities, such as hypertelorism, bony defects, and facial asymmetry.

The surgical approach to an encephalocele is typically open, but minimally invasive techniques such as endoscopic endonasal surgery can be employed when the encephalocele involves the sphenoid or ethmoid regions. This approach offers a favorable risk-benefit profile with a relatively low postoperative CSF leak rate.[14][55] The endoscopic repair complication rate of 14% compares favorably to the greater than 20% rate reported for open procedures.[38] However, 5% to 9% recurrence rates have been reported after endoscopic procedures, occasionally necessitating revision surgery.[14][56](A1)

The timing of surgical repair depends on factors such as the size and location of the lesion, associated complications, and whether the lesion is covered by skin. Surgery may be safely delayed for several months or even years for skin-covered encephaloceles, depending on the patient’s overall condition and the absence of acute complications. In contrast, non–skin-covered encephaloceles require urgent surgical intervention to prevent life-threatening infections such as meningitis or encephalitis, a management approach similar to other open NTDs. Basal encephaloceles, in particular, warrant early surgical correction to mitigate the risk of infection and to prevent progressive herniation of intracranial contents.[20]

Surgical repair of sincipital or basal encephaloceles involves weighing the challenges of low blood reserve in small children and technical anatomical difficulties against the risks of facial deformity, airway compromise, and infection. Some experts recommend deferring surgery until the child reaches 2 to 3 years of age if there is no active rhinorrhea or life-threatening condition. This delay allows for growth, making the procedure technically easier. However, others advocate for surgery as early as 2 months, as the nasal expansion caused by the encephalocele at this age can reduce surgical challenges.[38]

Repairing the dural defect is essential in all cases and can be performed primarily using pericranium, often reinforced with fibrin glue for additional stability.[21] Closure of the bony defect may involve autologous split calvarial bone grafts, titanium mesh, or osteoconductive bone material, although small defects may not require repair.[20] Intraoperative lumbar drainage for 5 to 7 days is often used to prevent postoperative CSF leaks.[20] Postoperative CSF leaks are reported in up to 6% of cases but typically respond well to lumbar drainage.[14] Reexploration for persistent CSF leaks is rarely needed, occurring in only 1% to 2% of cases.(A1)

Differential Diagnosis

The differential diagnoses for encephalocele include: 

• 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, including the location, size, amount of herniated brain, vascular involvement, and the presence of the hydrocephalus.[15][57] The prognosis is better for patients with frontoethmoidal encephaloceles than those with occipital or parietal encephaloceles. The prognosis also depends on the presence of additional congenital anomalies in the brain. A study evaluating clinical predictors showed that hydrocephalus and the presence of other intracranial abnormalities were significant predictors for developmental delay on multivariable analysis.[9] Their univariate analysis showed that seizure disorder, microcephaly, and brain tissue in the sac were significantly associated with poor outcomes.[9] Hydrocephalus has been documented in 34% of all patients before surgical repair of the defect, while it develops in 4% after the defect is closed.[13]

Long-term evaluation of children with encephaloceles has shown that 48% had adequate development, 11% had mild impairment, 16% had moderate impairment, and 25% had severe impairment.[9] Occipital encephaloceles carry a worse prognosis than frontal encephaloceles due to a higher incidence of seizures and hydrocephalus.[41] Approximately half of the patients with occipital encephaloceles are unable to live independently in society.[41] 

Factors that increase mortality include low birth weight and multiple intracranial defects; Black patients are also at increased mortality risk.[15] In a large series, mortality has been reported between 4% to 30%.[13][14][58] Approximately 76% of deaths occur on the first day of life, and roughly 71% survive to 1 year, with 67% living to 20.[15]

Complications

Structural abnormalities, associated anomalies, or surgical interventions can complicate encephaloceles. These complications vary depending on the herniation's size, location, and contents and can affect neurological, functional, and cosmetic outcomes.

Neurological Complications

Hydrocephalus: occurs in 40% to 60% of occipital encephaloceles and approximately 14% of frontal encephaloceles. This complication is often associated with neural tissue in the sac or other cranial anomalies, such as Chiari or Dandy-Walker malformations.

Seizures: are more common in occipital encephaloceles (17%) compared to sincipital or basal lesions. Temporal encephaloceles are associated with medically refractory epilepsy, especially when linked to idiopathic intracranial hypertension.

Developmental delay and cognitive impairment: are frequently observed in patients with larger encephaloceles or those lesions involving significant brain herniation.

Motor deficits: spasticity can occur in large posterior encephaloceles that include substantial brain tissue.

Visual impairments: occur if the encephalocele affects the optic apparatus; this is especially common in basal encephaloceles.

Infections

Meningitis and encephalitis: non–skin-covered encephaloceles and CSF leaks significantly increase the risk of central nervous system infections.

Recurrent infections: are particularly common in basal encephaloceles presenting with recurrent rhinorrhea or otorrhea.

Functional Issues

CSF leak: a common complication that can occur pre- or postoperatively. Postoperative CSF leaks are documented in up to 6% of cases and may necessitate lumbar drainage or revision surgery.

Nasal obstruction: common with basal encephaloceles involving the nasal cavity, leading to breathing difficulties or snoring.

Endocrinopathies: transsphenoidal encephaloceles containing the pituitary gland may result in hypopituitarism or other hormonal imbalances.

Surgical Complications

Blood loss: significant blood loss is a concern in small children due to their limited blood reserves.

Incomplete repair: failure to achieve watertight dural closure or stable bony reconstruction may result in recurrent herniation or persistent CSF leaks.

Injury to neurovascular structures: intraoperative injury to critical structures such as cranial nerves or vasculature can result in long-term deficits.

Recurrence: endoscopic approaches have reported recurrence rates of 5% to 9%, requiring revision surgery.[14][56]

Cosmetic and Structural Complications

Facial deformity: hypertelorism, orbital dystopia, or asymmetry may persist, particularly in extensive cases requiring craniofacial reconstruction.

Skull defects: inadequate repair of bony defects may lead to persistent cosmetic concerns or vulnerability to trauma.