Definition

These lesions are protrusions of brain contents through a congenital (or traumatic) defect in the skull base. A meningocele contains meninges and cerebrospinal fluid (CSF) alone, a meningoencephalocele contains brain tissue as well and rarely a ventricle may also be involved (meningoencephalocystocele). If no bony defect is present, then the mass containing heterotopic brain is termed a glioma.

Etiology

Several theories have been proposed but in general the frontonasal lesions probably result from a failure of the foramen cecum to close,2 allowing extrusion of intracranial contents (Fig. 15.1). In general it may be regarded as a form of neural tube defect and the frequency of these defects might therefore be anticipated to reduce with folic acid supplementation.3

Even when glial tissue is apparently isolated from intracranial structures, a fibrous stalk may be found in 15% of cases.4

In the lateral sphenoid, it has been suggested that an embryological failure of Sternberg′s canal to close leads to the bone deficiency, which is usually associated with an extensively pneumatized sinus.5 Here the temporal lobe prolapses, as opposed to frontal lobe, through the anterior defects. A range of other congenital anomalies and syndromes has been described in association with these defects, but usually they occur alone.

Synonyms

A variety of terms may be found for gliomas including glial ectopia, encephaloma, and—perhaps most appropriately—vestigial encephalocele.6 However, these lesions should not be regarded as tumors as they are nonneoplastic in origin and behavior.

Incidence

Initially described by Berger in 1890,7 these lesions were reported in increasing numbers in the 1960s and 1970s,8,9 making this a well-recognized condition. However, the incidence has now been shown to range from 1:10,000 live births in the United States to as high as 1:3,000 in South-East Asia. The reason for this geographical distribution is not known. No sexual predilection has been described.

Site

Encephaloceles are generally classified according to theirsite (Table 15.2).10 Anterior (or sincipital) defects are less common than those found in the occipital region (15% vs. 85%) but more common in Asia. In a series of 257 patients from Cambodia who presented in a 5-year period, the nasoethmoid region was most commonly affected (69%) and there were associated ophthalmological problems in 46% of cases.11 In the European literature the two common sites for congenital defects are at the vertical attachment of the middle turbinate and within the sphenoid. Multiple encephaloceles, although rare, can also occur.12

It has been estimated that ~25% of gliomas occur posterior to the nasal bone as intranasal lesions, 60% as sub-cutaneous lesions anterior to the nasal bone, and the rest as combinations of the two. Isolated glial tissue has also been reported elsewhere in the upper respiratory tract, including the nasopharynx, paranasal sinuses, and palate.

Diagnostic Features

Clinical Features

The majority of lesions are diagnosed at birth or during early childhood they but may occasionally remain undetected until adulthood, when they may present with a “spontaneous” cerebrospinal fluid leak.

Differential diagnosis of undifferentiated/poorly differentiated neoplasia of the sinonasal tract with immunophenotype

Tumor	CK	NSE	SYN	CHR	S100	HMB45a	LCA	Desmin	MYO	FLI	CD99	EBVb
SNUC		+c	+c	+c	–	–	–	–	–	–	–	–
SCC			+d	+d	–	–	–	–	–	–	–	–
NPUCe	+	–	–	–	–	–	–	–	–	–	–	+
ONB	–f				+g
Melanoma	–	–	–	–	+	+	–	–	–	–	–	–
Lymphomah							+			–i	–i	–j
RMS	–	–	–	–	–	–	–	+	+	–	–	–
PNET	+k –	+	+ –	–	+ –	–	–	–	–	+	+	–
PA	+	+	+	+	–	–	–	–	–	–	–	–
MC	–	+	–	–	+	–	–	+ –	–	–	+	–
Abbreviations: CHR, chromogranin; CK, cytokeratin; EBV, Epstein-Barr virus; LCA, leukocyte common antigen; MC, mesenchymal chondrosarcoma; MYO, myogenin; NPUC, nasopharyngeal undifferentiated carcinoma (lymphoepithelioma, etc.); NSE, neuron specific enolase; ONB, olfactory neuroblastoma; PA, pituitary adenoma; PNET, peripheral neuroectodermal tumor; RMS, rhabdomyosarcoma (embryonic and alveolar); SNUC, sinonasal undifferentiated carcinoma; SCC, small cell carcinoma; SYN, synaptophysin.
Source: From Strelow and Mills, reference 1 with permission from Lippin Cott, Williams & Wilkins.
a Or other specific melanocytic markers.
b EBV status may be assessed by a variety of means including in situ hybridization.
c Markers for neuroendocrine differentiation tend to stain SNUCs focally.
d SCCs may frequently lack staining for more specific endocrine markers.
e Also known as nonkeratinizing squamous cell carcinoma.
f ONBs may show focal immunoreactivity with antibodies to CKs.
g S100 immunoreactivity in ONBs is limited primarily to peripheral staining of the sustentacular cells.
h Including most of the hematological malignancies that may be found throughout this area (e.g., extranodal natural killer/T-cell lymphoma, nasal type, plasmacytoma).
i Lymphoblastic lymphomas often react with antibodies to CD99 and FLI1.
j Most lymphomas will not show diffuse, strong in situ hybridization for EBV-related nucleic acids or immunoreactivity with antibodies to EBV-related proteins. The notable exceptions include posttransplant lymphoproliferative disorders and extranodal natural killer/T-cell lymphoma, nasal type. In such patients, other markers may be needed.
k PNETs can sometimes show limited immunoreactivity with antibodies to low–molecular weight keratins.

Classically the child presents with a visible mass in the glabellar region which, if it is an encephalocele, commonly enlarges with crying or jugular compression (positive Furstenberg sign)4 or may be compressible or pulsatile (Table 15.3). An extranasal glioma simply presents as a mass, which can be covered with normal skin or have a bluish tinge. It does not change with crying or increased intracranial pressure.

Intranasal lesions produce unilateral obstruction (or bilateral depending on the size and site) and the visible mass on endoscopy, or even anterior rhinoscopy, may be pulsatile. Such lesions should never be biopsied without prior imaging as this will risk a CSF leak and/or meningitis. A CSF leak may of course be present ab initio.

The mass may expand the nasal bridge and in extreme cases, at birth, the size of the mass may necessitate emergency intervention to secure the airway in a facultative nose breather.

A mass may be seen on endoscopic examination but the mass may be fused with the septum and/or lateral wall of the nasal cavity and covered with mucosa and so not necessarily appear as a circumscribed “polyp.” Sometimes the lesion is too small to be seen easily or is hidden within a sinus (Figs. 15.2a, 15.3a).

Classification of encephaloceles

Classification	Site of herniation	Location of mass
I. Frontal
Sincipital
1. Nasofrontal	Fonticulus nasofrontalis	Forehead: nasal bridge
2. Nasoethmoidal	Foramen cecum	Nasal bridge
3. Naso-orbital	Medial orbital wall	Orbit
Basal
1. Transethmoidal	Cribriform plate	Intranasal
2. Sphenoethmoidal	Between ethmoid and sphenoid	Nasopharynx/ethmoid/sphenoid
3. Transsphenoidal	Craniopharyngeal canal	Nasopharynx/sphenoid
4. Sphenomaxillary	Superior and inferior orbital fissure	Pterygopalatine fossa
II. Occipital
Source: After reference 10.

Differential between glioma, meningoencephalocele, and dermoid cysts

	Glioma	Meningoencephalocele	Dermoid
Age	<5	<5 though can present as adult	Any age
Pulsation	No	Yes	No
Variable size, e.g., with crying	No	Yes	No
Texture	Firm	Soft	Variable
Patent intracranial connection	No	Yes	Possible
Neurons	No	Yes	No
Skin adnexal structures	No	No	Yes
Source: After reference 26.

Other clinical findings may be present as part of a more generalized skull base deformity, for example, optic nerve or endocrine disturbances.13,14 In later life, the individual may present with meningitis and/or with unilateral watery rhinorrhea due to the CSF leak. These “spontaneous” leaks are most often seen in obese individuals, most often women,15 and are frequently high flow. They can be multiple, making them difficult to manage.

Several protocols have been developed to assess suspected CSF leaks (Fig. 15.4); these consider confirmation of CSF rhinorrhea by the presence of β₂-transferrin or beta-trace protein (prostaglandin D₂ synthase) and determination of the site(s) of leakage by imaging.16–19 β₂-Transferrin analysis has been available since 1979 using electrophoresis by immunofixation or immunoblotting. A minimum volume of 2 µL is required and the test takes 2 to 4 hours. Beta-trace protein has been detectable by laser nephelometry since 2001 and requires a slightly greater volume (5 µL) but is a quicker test20 with a somewhat higher sensitivity and specificity.

In difficult cases intrathecal sodium fluorescein can be employed intraoperatively.21 Certain maneuvers and precautions are required such as a blue light and a blocking filter, but the dye can be detected at 1 in 10 million parts and complications are extremely rare. It can also help to visualize whether or not a CSF-tight closure has been achieved intraoperatively.22 The intrathecal fluorescein test can give a false-negative result, when for instance the defect site is blocked by edema of the mucosa, hematoma, or brain herniation; also, the injection technique can be faulty, timing and patient positioning may be inadequate, or the CSF circulation may be interrupted. However, intrathecal fluorescein cannot yield false-positive results.

Only a 5% aqueous sodium fluorescein solution, sterile and free of pyrogens, should be used. No other potentially neurotoxic substances like stabilizers and/or preservatives must be added. Intrathecal application is an off-label use of fluorescein for which informed consent must be obtained from the patient. Recommendations are to inject 0.05 to maximally 0.1 mL per 10 kg body weight; in no case, however, should more than 1.0 mL be given, even in a massively overweight patient. Fluorescein is injected via a standard lumbar puncture. In cases with evident CSF flow, it is administered a few hours or immediately prior to surgical intervention; in unclear or intermittently leaking cases, usually the evening before an intervention (Table 15.4). These techniques have superseded the use of radioactive dyes.

Fluorescein protocol for CSF leaks

Day before operation	Skin test patient with fluorescein (Minims eye drops 2%)
Informed consent	Grand mal seizures, cranial nerve palsies, opisthotonus
Day of operation	10 mg IM Piriton (chlorpheniramine/chlorphenamine) followed 5 min later by IV 10% fluorescein 0.25 mL diluted to 0.5 mL with water for injection
	Approx. 20 min later intrathecal injection of 0.2 mL 10% fluorescein made up to 7.5 mL with CSF (25G spinal needle)
	Patient goes to recovery (or ward) with head of bed down for approx. 90 min
	Patient undergoes normal anesthetic as for endoscopic sinus surgery
Postoperatively	If required, spinal drain inserted lumbar ¾ 16G epidural catheter. Drainage 5–10 mL per hour plus neurologic observations for 24–48 hours

While the diagnosis is being established, immunization against Meningococcus, Pneumococcus, and Haemophilus spp. is often recommended if not already given.

Natural History

Apart from the cosmetic and functional issues posed by these lesions, left untreated the patient remains at risk of meningitis (and CSF leakage) so treatment is recommended in the absence of any confounding factors.

Treatment

In the past, a neurosurgical approach was undertaken but endonasal endoscopic techniques are usually first choice for the majority of lesions. Exceptions would be when they are part of other more complex cranial base anomalies, in the case of extremely large defects, and when there is an extranasal component. Endonasal endoscopic surgery allows complete removal of the redundant tissue, accurate delineation of the defect, and a range of choices for repair materials.

The neural contents of the cele are regarded as redundant and the sac can be shrunk down considerably with endoscopic diathermy and then removed flush with the defect in the anterior skull base (Fig. 15.3a). Considerable care is required, however, in the sphenoid where the sac is often intimately related to the optic nerve and carotid artery and other vital structures in some congenital anomalies. The area of the defect needs to be well exposed and denuded of mucosa, which may require skeletonization of quite a large area of the skull base, including a complete ethmoidecomy and removal of the middle turbinate (which is a useful source of graft mucosa). In lesions of the sphenoid and pterygoid region wide exposure is the key to success, so a far-lateral removal of the face of the sphenoid and transpterygoid approach can be required (Figs. 15.2b, 15.6d).27,28

The endoscopic repair of skull base defects has generated a large literature, but in summary the choice of material is largely determined by the size and site of the defect and surgical preference.29 A meta-analysis of 35 of the major publications on this topic covering 1,123 patients30 failed to show any advantage for one material over another from a long list of possible choices, although free grafts of fascia and cartilage in combination with mucosa are most often used. Pinna cartilage will often slot into the funnel shape of some congenital defects, and fat as a “bath plug” can also be very useful in certain circumstances.31 Larger defects may benefit from a vascularized flap such as that described by Haddad and colleagues in 2006 that enables larger areas of septal mucosa to be utilized and is based on branches of the sphenopalatine artery.32

The technique may be underlay, onlay, or combination thereof; all have been used and there is general agreement that a two- or three-layer closure is required for congenital defects. The use of packing, postoperative medication, and bed rest varies from center to center and might also include antibiotics, antiemetics, and diuretics (e.g., acetazolamide) in the presence of raised intracranial pressure. Similarly, there is no consensus about the use of lumbar drains, although generally they are not used in primary cases unless the CSF leak is high-flow and well established. Occasionally in these cases—often the “spontaneous” leaks—a more permanent lumbar-peritoneal drain may be needed.

Subcranial or transcranial approaches are sometimes needed for extensive lesions or those also involving the orbits.

External glial lesions can sometimes be accessed via an external rhinoplasty or midfacial degloving approach in young children, but sometimes an accompanying external incision/excision may be required.

Outcome

Outcome will depend on many factors, including the size and site of the lesion, the presence of other abnormalities, and whether the aberrant CSF metabolism rectifies itself without additional intervention. Some very extensive encephaloceles may threaten survival and others have long-term mental or neurological deficit. Overall, the results for the anterior lesions are better than for occipital lesions and those within the anterior skull base; the sphenoid lesions are the most difficult, particularly in the adult “spontaneous” group.

Most series of endoscopic repairs include a heterogeneous group of congenital and acquired lesions of different extents, sites, and durations, but in general results are good, with primary closure rates of 90% and better. Follow-up ranged from 1 to 162 months and recurrence occurred between 2 days and 18 months, although it tended to occur within the first few weeks and months.30 However, 50% success was reported specifically for sphenoid sinus defects and 50% of “spontaneous” leaks overall.33 In cases of primary failure, a second endoscopic attempt was definitely worthwhile, with success rates of 93 to 100%. External craniotomy remains an option for the most difficult cases but this also cannot guarantee success and carries a somewhat higher morbidity due to frontal lobe retraction and anosmia.34,35

In contrast, gliomas by their nature do not recur after complete excision. Rahbar et al10 reported 10 patients with nasal glioma, mean age 9 months, who were successfully treated without complication and a mean follow-up of 3.5 years.