Cephalocele

Protrusion of intracranial contents through a defect in the skull. The term cephalocele is an umbrella term that describes all types of herniation. The specific subtype is determined by the type of tissue that herniates through the skull defect. The defect is usually covered by intact skin.

Encephalocele, cephalocele, cranial or occipital meningocele, cranium bifidum, encephalomeningocele, encephalocystocele, encephalomeningocystocele.

ICD-10: Q01

Cephaloceles occur in 8:10,000 births. Differences in type and frequency among various ethnic groups have been described. In the Western hemisphere the incidence is 1 to 3 per 10,000 births. In Southeast Asia the incidence is slightly higher, in the range of 1 in 5,000 live births. Occipital cephaloceles are most common in populations of European extraction, while frontal cephaloceles are 5‑12 times more common than other cephaloceles in populations of Southeast Asian descent.

Neural folds develop at around 20 days after conception. They fuse anteriorly and develop optic and olfactory nerves. Around 44 days, cranial ossification begins, proceeding dorsally and posteriorly. It is likely that the insulting event which will result in development of a cephalocele occur at least by day 45‑50. Theories include neural ectodermal maldevelopment (failure of anterior fusion of the neural folds with resulting failure of skull formation), as well as mesodermal maldevelopment (herniation of brain through bony malformation).^2-4

Cephaloceles are heterogeneous disorders. Occipital cephaloceles are generally considered part of the neural tube defects spectrum (including anencephaly, iniencephaly, spina bifida), which are multifactorial in nature. Occipital cephaloceles may also occur as part of several genetic and non-genetic syndromes (see Table 1). Frontal cephaloceles, by contrast, are not associated with increased neural tube defect risk in relatives and show possible environmental causation, especially in Southeast Asia. Cephaloceles can be experimentally induced by teratogens like x-rays, trypan blue, or hypervitaminosis A. Maternal obesity has recently been shown to be a risk factor.

Autosomal dominant Dandy-Walker malformation with occipital cephalocele (ADDWOC) is a rare genetic condition caused by novel mutations in NID1 and LAMC1 genes, indicating genetic heterogeneity in cephalocele syndromes.

Cephaloceles are classified by content and location:

• Meningocele: meninges only
• Encephalocele: brain tissue only
• Encephalomeningocele: meninges and brain tissue
• Encephalomeningocystocele: meninges, brain tissue, and lateral ventricles

By site:

• Occipital: defect between lambdoid suture and foramen magnum
• Parietal: defect between bregma and lambda
• Anterior: defect between bregma and anterior ethmoid, subdivided into frontal, sincipital, and basal types

Frontal cephaloceles are external, near the nasal root (glabella), subdivided into nasofrontal, nasoethmoid, and naso-orbital types. Basal cephaloceles are internal lesions occurring in nose, pharynx, or orbit.

An atretic cephalocele variant is characterized by a small cystic lesion without brain tissue, usually covered by skin and associated with a skull defect, with a favorable prognosis and typically no other CNS anomalies.

An unusual case of an anterior double cephalocele was reported at 12+3 weeks’ gestation, where two bulging structures were noted in the nasofrontal region: one a meningoencephalocele containing brain tissue and fluid, and the other possibly a meningoencephalocystocele or ventriculocele with herniated choroid plexus through a skull defect. This highlights that cephaloceles may present with complex variations in morphology detectable early in gestation.

Cephaloceles are frequently associated with other cerebral and cranial malformations including ventriculomegaly (60-80% of occipital cephaloceles and 15% of frontal ones), microcephaly¹ and spina bifida.¹⁰ Displacement of the cerebellum inside the cephalocele is occasionally observed and it is referred to as the Chiari type III deformity. This deformity, combined with aqueductal stenosis, is the major cause of hydrocephalus in these infants.^{2, 3} Cephaloceles are often part of specific syndromes (Table 1). Meckel-Gruber syndrome (dysplastic cystic kidneys, cephalocles and/or other cerebral malformations, polydactyly) is particularly frequent in prenatal series.11 Another noteworthy condition is Walker-Warburg syndrome (WWS) – an autosomal recessve dystroglycanopathy characterized by cobblestone lissencephaly, eye abnormalities, congenital muscular dystrophy, and profound brain malformations. Cephaloceles — particularly occipital — are well-described associated findings in WWS, reflecting the underlying disruption of basement membrane integrity and abnormal skull / neural tube formation.

Frontal cephaloceles are often associated with the median cleft face syndrome, characterized by hypertelorism and median cleft lip or palate.^{6, 12-14} Chromosomal aberrations have been described as well, mostly in prenatal studies.^{10, 15-18} In a large series of non-syndromic cephaloceles the most common malformations were ventricular septal defect, gastroschisis, fetal pyelectasia and diaphragmatic herniation.

Some genetic syndromes are associated with a high risk of recurrence.¹¹ Non-syndromic cephaloceles are probably related to neural tube defects at least in some cases, and probably share in common with these a multifactorial etiology.²⁰

A cephalocele is suspected prenatally when a paracranial mass is seen on ultrasound. Encephaloceles are easier to diagnose due to brain tissue visibility. Differentiating meningoceles from scalp cysts or neck cysts can be difficult. Basal cephaloceles are internal (into the nasal cavity / sphenoid sinus) and are often not obvious on standard prenatal ultrasound. They may be detectable with targeted high-resolution neurosonography, but MRI is typically superior for confidently identifying them.

First-trimester detection of cephaloceles is feasible with detailed assessment of skull contour during routine axial and sagittal ultrasound views performed for biparietal diameter and nuchal translucency measurements. An encephalocele will also result in abnormal intracranial anatomy, visible on standard brain views obtained during the nuchal translucency scan. Doppler studies can help as a finding of a persistent falcine sinus in a fetus with a cephalocele suggests abnormal posterior fossa venous drainage and should prompt careful evaluation of the torcular region with color Doppler and MRI.

Alpha-fetoprotein levels are usually normal due to intact skin coverage.

Serial examination of fetuses with cephaloceles has demonstrated that the sonographic appearance of the lesion may change throughout gestation. Transition from a solid to a fluid pattern and transient disappearance has been described.

Progression of herniation is reported in about 50% of fetal cephalocele cases. Risk factors include fetal hindbrain herniation and microcephaly. Larger sac volumes are associated with higher risk of continued herniation postnatally.

Occipital meningocele must be differentiated from cystic hygromas. Demonstration of the bony defect in the skull would allow a proper diagnosis 23 but cranial meningoceles are often associated with extremely small defects that are difficult to recognize with antenatal ultrasound. Indirect clues can assist the diagnosis. Cranial cephaloceles are very often associated with other abnormal findings, similar to those encountered with open spina bifida, such as ventriculomegaly, microcephaly, and obliteration of the cisterna magna.³⁹ Other intracranial anomalies anomlies commonly seen are corpus callosum anomalies, cortical aniomalies (i.e heterotopias and polymicrogyria) and dural venous sinus anomalies.

Cystic hygromas arise from the region of the neck and have a large base, may have multiple internal septations and be associated with generalized soft tissue edema and hydrops. Small meningoceles of the cranial vault must be differentiated from scalp cysts and other soft tissue lesions such as unilocular cystic hygromas and hemangioma.^{26, 29, 31, 31, 34} Although a certain diagnosis may be impossible at times, demonstration of a seemingly intact calvarium and normal brain anatomy strongly suggests a soft tissue lesion.

The differential diagnosis of frontal cephaloceles includes midline soft tissue lesions such as nasal gliomas, hemangiomas, dermoid cyst and dacryocystocele.^{27, 28, 33, 35}

Basal cephaloceles protruding through the mouth must be differentiated from rare oral tumors such as epignathus.

Cephaloceles should be suspected when a paracranial mass is seen. Intracranial anomalies such as ventriculomegaly are also frequently seen. Small cephalocele in an atypical position, particularly developing through the base of the skull will probably escape detection if they are not associated with abnormal intracranial anatomy. A large series demostrated that a sonographic diagnosis is made in most, although not in all, cases. The EUROCAT registry reports that in the years 1995-1999, a prenatal diagnosis was made in 79% of cases and 66% of pregnancies were terminated. 

Most cephaloceles will be rapidly identified as paracranial masses. In some cases however the diagnosis may not be obvious. Differential diagnosis from soft tissue lesions of the head may be difficult at times. Evaluation of the integrity of the fetal calvarium and brain anatomy is the most important clue.

Outcome varies widely, depending on type, site, extent, associated abnormalities and underlying genetic disorders. Mortality is higher when significant brain tissue protrudes externally. Intellectual development is more likely impaired with brain involvement and hydrocephalus. Posterior defects generally have poorer prognosis than anterior defects.

Imaging features associated with poor prognosis in occipital cephaloceles include involvement of the cerebellum, occipital lobes, and microcephaly. These parameters aid in counseling families about survival and developmental outcomes.

TABLE 1.  Imaging score for evaluation of teal MRI for predictors of post-natal course and prognosis in patients with occipital cephalocele.

TABLE 2. Cephalocele grading system for evaluation of fetal MRI for predictors of post-natal course and prognosis in patients with occipital cephalocele.

A higher imaging score and cephalocele grade, as defined by this study, were associated with greater mortality and delays in both verbal and motor development.

Anatomic survey to search for associated anomalies and chromosomal analysis are indicated. Termination of pregnancy before viability is an option. In continuing pregnancies, obstetrical manage­ment depends on the amount of herniated brain tissue, and associated anomalies. Theoretically, a cesarean section could improve prognosis by avoiding birth trauma and contamination of brain tissue with vaginal flora.¹⁰ 

Some cephaloceles are a part of the spectrum of neural tube defects and may be prevented by folic acid supplementation. The reader is referred to the sections on spina bifida and anencephaly.

Amniotic band syndrome (sporadic)

Multiple cephaloceles, predominantly anterior

Amputations of digits or limbs

Bizarre oral clefts Chemke syndrome (AR)

Hydrocephaly

Agyria

Cerebellar dysgenesis Cryptophtalmos syndrome (AR)

Forehead skin covers one or both eyes

Ear abnormalities

Soft tissue syndactyly Dyssegmental dysplasia (AR)

Short limb dysplasia

Metaphyseal widening

Small thorax

Micrognathia

Frontonasal dysplasia (sporadic, some cases are familial)

Frontal cephalocele

Ocular hypertelorism Meckel syndrome (AR)

Polycystic kidneys

Polydactyly

Microphthalmia

Orofacial clefting

Ambiguous genitalia von Voss syndrome (?)

Agenesis of the corpus callosum

Phocomelia

Urogenital anomalies

Thrombocytopenia Warfarin syndrome

Nasal hypoplasia

Bone stippling

Limb shortening

Hydrocephaly

Associations

Absence of corpus callosum

Cleft lip or palate

Cleft lip-palate

Craniostenosis

Dandy-Walker syndrome

Ectrodactyly

Hemifacial microsomia (see microphthalmia section)

Iniencephaly

Meningomyelocele

AR, AD autosomal recessive, autosomal dominant

Modified from Cohen, Lemire: Teratology 25:161, 1982.

Tavares de Sousa, M., Gonçalves, Â., & Montenegro, N. (2021). Unusual double anterior cephalocele. Ultrasound in Obstetrics & Gynecology, 57(4), 630–632.
 

Lakshmanan, P., Radhakrishnan, A., Sundararajan, N., & Ramachandran, A. (2022). Atretic cephalocele: A rare neural tube defect. Journal of Pediatric Neurosciences, 17(2), 131–133.
 

Gupta, N., Mohr, A., Bhatia, S., & Whitehead, W. E. (2022). Predictors of progressive herniation in fetal encephaloceles. Journal of Neurosurgery: Pediatrics, 30(6), 676–683.
 

Chang, K., Hill, A., & Whitehead, W. E. (2024). Sac volume and neural herniation risk in fetal cephaloceles. Journal of Neurosurgery: Pediatrics. Advance online publication.
 

Syngelaki, A., Chelemen, T., Dagklis, T., Allan, L., & Nicolaides, K. H. (2011). Challenges in first-trimester diagnosis of cephalocele. Ultrasound in Obstetrics & Gynecology, 38(5), 513–516.
 

Griffin, N., Vargas, M. I., & Millischer, A. (2022). Imaging predictors of perinatal outcome in fetal occipital cephaloceles. Prenatal Diagnosis, 42(5), 585–592.
 

Gonçalves-Ferri, W. A., San Martin, S., & Palhares, D. B. (2021). Cephalocele and prenatal intracranial hypotension: Implications for diagnosis. Prenatal Diagnosis, 41(6), 725–732.
 

Darbro, B. W., Guter, S., Murphy, L., Dugan, P., & Kolbe, D. (2023). Autosomal dominant Dandy–Walker malformation with occipital cephalocele caused by a novel NID1 variant. European Journal of Medical Genetics, 66, 104713.

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