Abstract
Cerebrospinal fluid (CSF) leaks at the skull base have gained attention over the last several decades as potential sources of morbidity, particularly after traumatic injury. The present study discusses the relevant anatomy and imaging modalities for the accurate identification and characterization of CSF leaks, with an emphasis on noninvasive imaging including high-resolution computed tomography and magnetic resonance cisternography.
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Keywords
- CSF leak
- High-resolution computed tomography
- Magnetic resonance imaging
- Magnetic resonance cisternogram
- Computed tomography cisternogram
- Idiopathic intracranial hypertension
Introduction
A skull base cerebrospinal fluid (CSF) leak describes the egress of CSF from the intracranial subarachnoid space into the extracranial space via an osteodural defect, most commonly at the sinonasal or tympanomastoid cavities [1]. Leakage of CSF into either the nose or the ear, coined CSF rhinorrhea or otorrhea, was identified as pathologic entities over a century ago with a wide range of potential etiologies, including post-traumatic, surgical, neoplastic, and spontaneous causes. Subsequent decades have shown increasing recognition for the clinical importance of CSF leaks as sources of significant potential morbidity and mortality, with persistent CSF rhinorrhea carrying a 10 to 37% lifetime risk for meningitis [2,3,4,5,6], as well as increasing risk for seizures, cranial neuropathies, and headache [7].
Given the potential long-term consequences of missed diagnosis, the timely and accurate identification of a suspected CSF leak is of tremendous clinical import. β2-Transferrin protein testing remains the mainstay for confirmation of any suspected case of CSF rhinorrhea or otorrhea with reported sensitivity ranging from 87 to 100% and specificity of 71 to 94% [7,8,9,10]. Once confirmed, imaging plays a critical role in determining the site of a suspected or confirmed CSF leak, often using a combination of high-resolution computed tomography (HRCT) and magnetic resonance (MR) imaging, with or without the use of intrathecal contrast agents. Beyond the identification potential routes of CSF leak, radiological evaluation can also aid in the diagnosis of any underlying causative etiology, such as spontaneous CSF leaks referable to idiopathic intracranial hypertension (IIH) or in the setting of skull base invasion from neoplastic or infectious etiologies [1, 7, 8, 11].
In the course of this chapter, we will review the imaging techniques used to diagnose and characterize the sites of CSF leak with an emphasis on noninvasive CT and MR imaging. We will highlight common imaging findings of confirmed CSF leaks and their causative factors, including traumatic, iatrogenic, and spontaneous leaks. We will then discuss potential mimics of CSF leak and common imaging pitfalls in this essential diagnosis.
Diagnostic Techniques
At our institution, initial imaging modalities in the evaluation of suspected or confirmed leaks are usually noninvasive, including high-resolution computed tomography (HRCT) and magnetic resonance cisternography (MRC). In complex or equivocal cases, more invasive techniques including computed tomography cisternography (CTC), contrast-enhanced magnetic resonance cisternography (CE-MRC), and radionuclide cisternography (RNC) are employed as problem-solving techniques (Table 5.1). Ultimately, the choice of imaging modality and diagnostic accuracy remains dependent on local experience, imaging expertise, and the technical capabilities at any individual institution.
Computed Tomography
High-resolution CT (HRCT) of the paranasal sinuses and skull base is often the first-line imaging modality of choice in the setting of suspected CSF leak due to its relative clinical accessibility and short acquisition time. HRCT performed using submillimeter acquisition affords exquisite spatial resolution and superior delineation of osseous detail, making it ideal to identify potential regions of dehiscence of the anterior and posterolateral skull base [12,13,14]. In a recently meta-analysis, 12 published studies reported HRCT sensitivity over 80% in the identification of the site of a β2-transferrin-confirmed CSF leak [7]. Moreover, a recent investigation indicated that the size of the defect can be accurately predicted on HRCT to within 2 mm in 75% of cases [12] assuming minimum collimation and the ability to general multiplanar reformats. Adding to the potential utility of this technique, the identification of osseous dehiscence by HRCT is not dependent on the presence of an active leak at the time of imaging, making it ideal for the investigation of subtle abnormalities or slow-flowing leaks [11, 15]. Furthermore, dedicated HRCT of the paranasal sinuses and skull base affords the surgeon a detailed view of the remainder of the sinonasal cavity for surgical planning and intraoperative navigation during endoscopic repair [12, 14, 16].
HRCT performed for the identification of CSF leak should include minimum detector collimation, thin-section (0.5 mm or 0.625 mm) acquisition utilizing bone algorithms [1, 11, 17]. In general, axial images are considered superior for the evaluation of the vertically oriented structures of the skull base, including the posterior frontal and lateral sphenoid sinuses and in the evaluation of the mastoid air cells (Fig. 5.1). In distinction, coronal images offer advantage in the assessment of the longitudinally oriented cribriform plates, planum ethmoidale, planum sphenoidale, and temporal tegmen (Fig. 5.1). As such, historical acquisition parameters have included both axial and direct coronal planes for improved in-plane resolution, requiring prone positioning of the patient, significant neck extension within the gantry, and increased radiation dosage. Modern multi-detector CT now involves rapid, continuous volumetric acquisition with isotropic voxels, allowing for the creation of high-quality, high-resolution coronal and sagittal reformats from a single axial acquisition [1, 11]. Unless the location of a CSF leak is known, a thorough work up of CSF rhinorrhea requires HRCT imaging of the anterior, central, and posterolateral skull base as CSF leaking into the middle ear cavity can present as rhinorrhea via egress through the Eustachian tubes [18]. Therefore, the authors recommend a field-of-view inclusive of the sinonasal cavity, anterior and central skull base, and temporal bones for complete evaluation of suspected or confirmed CSF rhinorrhea.
Relative disadvantages of HRCT include the inability to assess for a concomitant dural defect in the setting of multiple regions of osseous thinning at the skull base. HRCT is also limited in the ability to discriminate between adjacent mucosal thickening and secretions from a suspected CSF collection in the paranasal sinuses [11, 16]. These limitations may contribute to the wide ranges of specificity of HRCT in the detection of a CSF leak reported in the literature, ranging from 57 to 100% [7, 19]. However, if only single osseous defect is identified on HRCT corresponding to the clinical symptoms, the patient can proceed to surgical repair without further imaging [12, 14].
Magnetic Resonance Cisternography
Magnetic resonance cisternography (MRC) is often performed as an adjunct or even a stand-alone imaging study in the setting of confirmed CSF leak due to superior soft tissue resolution and ability to increase the conspicuity of CSF based on the imaging technique utilized. Most MRC protocols exploit heavily T2-weighted (T2W) 3D-fast (turbo) spin echo (e.g., T2 SPACE, T2 CUBE) or steady-state-free precession (SSFP) sequences to highlight the intrinsic T2 prolongation of CSF relative to the adjacent neural and osseous elements, as well as facilitating the creation of multiplanar reformats from submillimeter acquisition [11, 20] (Fig. 5.2). In this manner, MRC can not only confirm but also identify the site of a CSF leak by visualizing a contiguous CSF column extending through a defect in the floor of the anterior cranial fossa, tegmen tympani, or tegmen mastoideum. Collectively, studies report a sensitivity of 56–94% for CSF leak detection, with a specificity of 57–100% [7].
A further advantage of MRC relative to HRCT is the ability to identify herniation of the meninges or neural elements (e.g., meningocele or meningoencephalocele) in association with an ongoing CSF leak [1, 11, 14]. Underlying meningoencephalocele should be considered in the setting of a skull base defect with downstream opacification of an adjacent sinus or mastoid air cell, particularly if the opacification is lobulated or anti-dependent. Although differentiation between fluid opacification and neural elements is often difficult by CT, the superior soft tissue resolution of MR easily distinguishes brain parenchyma from CSF, helping to aid surgical planning prior to repair (Fig. 5.2). The use of additional fast-spin echo and fast spoiled gradient-echo sequences, particularly with intravenous contrast and fat suppression, can further help identify potential complications related to CSF, such as retrograde meningitis and encephalitis.
One limitation of MRC is its dependence upon the presence of an active leak at the time of imaging to successfully identify the region of communication between the intracranial and extracranial compartments. Coupled with an inherently lower spatial resolution of the osseous skull base, many authors advocate use of both HRCT and MRC, with a combined reported accuracy of 92–100% in the current literature [21,22,23].
Contrast-Enhanced Cisternography
In contrast to the previously described imaging methodologies, contrast-enhanced CT and MR cisternography are invasive techniques, requiring the administration of intrathecal contrast, usually via lumbar puncture in the fluoroscopy suite. With improvements in both HRCT and MRC, intrathecal contrast-based imaging is utilized as a problem-solving tool at our institution, reserved for complex or equivocal cases after other imaging modalities have been employed.
CT cisternography (CTC) was previously the gold standard in the evaluation of potential CSF leaks, but now is predominantly used as a problem-solving technique, particularly to help pinpoint the site of an active leak in the setting of multiple osseous defects [14, 24] (Figs. 5.3 and 5.4). CTC protocol involves obtaining HRCT in both the prone and supine positions through the region of interest before and after low osmolality intrathecal contrast material is introduced. One advantage to CTC is the ability to perform provocative maneuvers at the time of imaging, such as sneezing or head hanging, to attempt to improve delineation of a leak. Evaluation of the obtained imaging requires comparison of the pre- and post-contrast scans, with a positive result considered if there is an increase in the attenuation of an opacified structure (sinus, nasal cavity, middle ear, etc.) adjacent to a skull base defect 50% or more above the baseline on the noncontrast examination [14]. The utility of a CTC is limited to patients in whom an active leak is present or elicited by provocative maneuvers. Additional pitfalls of this technique can include obscuration of small leaks by adjacent sclerotic changes of the paranasal sinuses or high-density, inspissated secretions, as well as the presence of blood. In combination, these factors may account for some degree of the disparity of reported sensitivities, ranging from 33% to 100% [7, 19, 22].
Intrathecal, contrast-enhanced techniques can also be combined with the MRC technique, utilizing thin-section, T1-weighted sequences obtained in multiple planes after the administration of gadolinium-based contrast. Similar to CTC, a positive study demonstrates contrast extravasation through an osseous and dural defect of the skull base and must be interpreted in conjunction with HRCT. Studies have shown enhanced sensitivity for detection of CSF leaks compared to both HRCT and standard MRC, with up to 100% sensitivity for high-flow leaks and 60% to 70% sensitivity for slow-flow leaks [20, 25, 26]. Some of this improved sensitivity may stem from the ability to perform delayed imaging up to 24 h after gadolinium administration, which can be particularly useful in slow-flowing or intermittent leaks [26]. As with all MR-based protocols, superior soft tissue resolution and increased conspicuity of CSF afford the ability to detect concomitant meningoceles as well as improved discrimination of leaking contrast from adjacent sclerotic or hypertrophied bony structures compared to CTC. Although several studies indicate good safety data using low-dose intrathecal gadolinium in other countries, intrathecal administration remains an off-label use of gadolinium by the US Food and Drug Administration (FDA), and long-term safety studies are still pending. As such, given the invasive nature of the study, the known neurotoxicity of gadolinium in high doses, and current off-label use, selective employment of this technique as a problem-solving tool only is recommended and only after thorough off-label use consent.
Nuclear Medicine Cisternography
Radionuclide cisternography (RNC) is a nuclear medicine diagnostic examination involving the intrathecal administration of technetium-99 or indium-111 radiotracer. Multiple pledglets are introduced to the nasal cavity followed by placing the patient in the Trendelenburg position to facilitate craniad tracer flow [1, 16]. Pledglet radioactivity is measured after 24 to 48 h to confirm the presence of a CSF leak, with a positive study heralded by a pledglet to serum plasma tracer ratio of 2:1 or 3:1 [1]. RNC is limited to the detection of active leaks and only offers minimal, if any, information about leak location given the inherent mixing of nasal secretions from side to side and the possibility of CSF rhinorrhea stemming from an underlying temporal bone process [1, 11, 14]. For these reasons, and due to its invasive nature, RNC is only selectively employed at our institution as a problem-solving measure for CSF leak confirmation.
Imaging Findings of CSF Leak
Imaging hallmarks of CSF leak on HRCT include an osseous defect in the skull base associated with an air-fluid level or opacification of the contiguous sinus, mastoid air cells, or middle ear cavity. The most common location for a skull base CSF leak is at the cribriform plate although several additional locations are also commonly implicated, including the anterior ethmoid, posterior ethmoid, sphenoid, and frontal sinuses [1] (Fig. 5.5). CSF leaks from the temporal bone tegmen are relatively less common but should be included in imaging protocol as CSF leakage into the middle ear can also manifest as rhinorrhea via egress through the Eustachian tubes [11, 14, 18] (Fig. 5.5). Anterior skull base defects are usually adjacent to the vertical insertion of the middle turbinate or at the lateral lamella, although normal thinning of these structures can make specific leak site detection difficult [1]. Identification is aided by comparing to the contralateral side, scrutinizing for subtle associated pneumocephalus adjacent to a fracture line, as well as identifying asymmetric mucosal thickening or soft tissue opacification beneath a suspected osseous defect as the first sign of an underlying meningoencephalocele (Figs. 5.6 and 5.7).
As adjunct imaging, or in the case of suspected meningoencephalocele, MRC may further help localize the leak by identifying a contiguous CSF column extending through a deficiency in the skull base and adjacent dura (Fig. 5.6), although this is contingent upon an active leak being present at the time of imaging. Further multiplanar T1- and T2-weighted imaging of the skull base is essential to detect the presence of an underlying meningocele/meningoencephalocele. Other indirect signs of CSF leak can also be revealed by MR, including variable degrees of encephalomalacia associated with an ongoing leak [11] (Fig. 5.6), associated dural enhancement (in the case of concurrent intravenous contrast administration), as well as the identification of potential intracranial complications, including meningitis/cerebritis (Fig. 5.8). Contrast-enhanced CT and MR cisternography evaluations are both based on identification of extravasated contrast via an osteodural defect in the skull base, often quantified in comparison to pre-contrast images, as previously described.
With these general principles in mind, it is important to note that the imaging appearance of a CSF leak is dependent upon the underlying etiology, whether traumatic, iatrogenic, spontaneous, or secondary to underlying neoplastic, congenital, or infectious causes.
Traumatic CSF Leaks
The majority of skull base CSF leaks are associated with traumatic injuries, with 10% to 30% of skull base fractures complicated by concomitant CSF leak [14, 16, 27]. Tightly adherent dura along the inherently thin cribriform plates and planum ethmoidale/sphenoidale may explain the propensity for comminuted anterior cranial fossa fractures to result in CSF leak, although CSF from fractures of the posterior frontal sinus, lateral walls of the sphenoid sinus, or even the sella turcica have also been reported (Fig. 5.5). CSF leak frequency ranges from 11 to 45% of patients with underlying temporal bone fractures, more often in the setting of otic capsule violation [28]. Although displaced or comminuted fractures are rarely a clinical or diagnostic dilemma, subtle or nondisplaced fractures can be overlooked by routine CT; in this setting, the presence of intracranial pneumocephalus can be the first clue for a subtle osseous traumatic injury and should prompt careful interrogation of the adjacent skull base and/or repeat evaluation with HRCT (Fig. 5.5).
Iatrogenic CSF Leaks
CSF leak is a known complication of both neurosurgical and otolaryngologic procedures, with a reported overall incidence of 14% via endoscopic and endonasal approaches to the anterior and central skull base [29] (Fig. 5.9). As such, the timely reporting of variant anatomy of the anterior cranial fossa and central skull base is of critical importance on presurgical HRCT, including the Keros classification of the olfactory fossa and any associated asymmetry of the cribriform plate [30]. Variant sphenoid sinus pneumatization should also be reported, as well as any extension anteriorly into the clinoid process, laterally into the sphenoid wing, inferiorly into the pterygoid plate, or posteriorly into the clivus, as associated bony thinning can increase the risk of postoperative CSF leak [31]. Most iatrogenic leaks occur within the first 2 postoperative weeks and resolve spontaneously [14]; if repair is indicated, typically only preoperative HRCT is required as the location of the leak is assumed at the surgical site, although initial evaluation can be difficult in the immediate postoperative setting given adjacent post-surgical material and hemorrhage (Fig. 5.10).
Secondary CSF Leaks
In the absence of trauma or prior surgery, there are many additional potential causative etiologies of CSF leak at the skull base, including sinonasal or primary skull base malignancy (Fig. 5.11), prior radiation therapy/osteoradionecrosis, or congenital abnormalities, including encephaloceles, persistent craniopharyngeal canal, or primary empty sella syndrome.
Spontaneous CSF Leaks
The last several decades have seen increased prevalence of idiopathic intracranial hypertension (IIH), a headache syndrome characterized by supranormal intracranial pressure without clear cause, classically seen in overweight women associated with visual disturbance, papilledema, and other potential neurologic stigmata [32]. Spontaneous CSF leaks are becoming a frequent presentation of IIH and one of the most common indications for imaging in the setting of CSF leak [33, 34]. In this cohort of patients, it is proposed that elevated intracranial pressures leads to increased magnitude of dural pulsations, weakening the osseous skull base and resulting in multiple regions of thinning and dehiscence seen on HRCT [35, 36]. Loss of osseous integrity, coupled with elevated intracranial pressures, allows for the formation of multiple arachnoid pits/granulations and, eventually, dural tears with associated CSF leak. Although imaging findings are not in the diagnostic criteria for IIH, there are several MR imaging features that have been associated with IIH in the literature, including an expanded sella with a partially empty configuration, optic nerve sheath enlargement/tortuosity, flattening of the posterior globe, and/or papilledema [13, 37] (Figs. 5.12 and 5.13). Other works have described stenosis between the junction of the transverse and sigmoid sinuses as the most specific feature of IIH, although it remains unclear if this is a causative agent or secondary finding in this clinical diagnosis [38] (Fig. 5.12). Nevertheless, these imaging features in conjunction with clinical signs of papilledema and elevated opening pressure on lumbar puncture are strongly suggestive of the diagnosis of IIH. Given the propensity for multifocal regions of osseous thinning and the increased risk of meningocele/meningoencephalocele formation, patients with suspected or confirmed IIH often require multimodal imaging work up including both HRCT and MRC prior to any elective intervention.
Pitfalls and Mimics
There are numerous challenges in the imaging evaluation of patients with suspected or confirmed CSF rhinorrhea and otorrhea. Some of the more frequently encountered include:
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MRC, CTC, and contrast-enhanced MRC are dependent upon the presence of an active CSF leak at the time of imaging and, as such, may fail to detect intermittent or very-slow flow leaks at the time of imaging.
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Although HRCT can identify bony defects regardless of leak activity, thinning and irregularity of the skull base structures of the anterior and middle cranial fossa are a relatively common finding in the population in the absence of clinical concern for CSF leak.
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Particularly in the setting of IIH or polytrauma, multiple osseous defects, and even multiple meningoceles, may be present in one patient, making the identification of the true site of active leakage difficult on HRCT. MR cisternogram can be helpful in this setting, but can result in the occasional false negative if the patient is not leaking at the time of imaging. In these cases, consideration of CTC or contrast-enhanced MRC is recommended, potentially with provocative maneuvers or delayed imaging, as problem-solving tools for better localization.
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Evaluation of contrast extravasation using CTC in the postoperative setting can be obscured by other high-density components, including hypertrophied osseous structures, inspissated secretions/blood products, and granulation tissue. Comparison between pre- and post-contrast images and careful windowing using soft tissue algorithms can be helpful to discriminate between artifact and true egress of contrast.
Although there is no real differential diagnosis for an underlying CSF leak, there are several imaging findings on HRCT that may mimic the opacification pattern of a CSF leak, yet belie a more insidious process. Ostiomeatal unit pattern sinonasal inflammatory disease, particularly if long standing, can result in various degrees of neo-osteogenesis and osseous thinning, although intact periosteum may be in place in the absence of symptoms referable to CSF rhinorrhea. Both CSF leaks and malignancy can present as unilateral opacification of the sinonasal cavity; in this case, frank osseous destruction of the intervening bony boundaries can tip the radiologist toward a diagnosis of underlying malignancy, which is easily confirmed by MRI (Fig. 5.14).
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McDonald, M.A. (2023). Imaging for Detection of CSF Leaks. In: Kuan, E.C., Tajudeen, B.A., Djalilian, H.R., Lin, H.W. (eds) Skull Base Reconstruction . Springer, Cham. https://doi.org/10.1007/978-3-031-27937-9_5
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