Pathophysiology of skull base defects and cerebrospinal fluid leak

Saud Romaih Alromaih

doi:10.4103/sjoh.sjoh_52_20

REVIEW ARTICLE

Year : 2021 | Volume : 23 | Issue : 3 | Page : 91-94

Pathophysiology of skull base defects and cerebrospinal fluid leak

Saud Romaih Alromaih
Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia

Date of Submission	20-Nov-2020
Date of Acceptance	30-Nov-2020
Date of Web Publication	05-Oct-2021

Correspondence Address:
Dr. Saud Romaih Alromaih
P.O. Box 245, Riyadh 11411
Saudi Arabia

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/sjoh.sjoh_52_20

Abstract

Cerebrospinal fluid (CSF) leak is a rare pathology with many etiologies. It can be spontaneous, congenital, iatrogenic, or traumatic [Figure 1]. A skull base defect may occur along the anterior or lateral skull base manifesting as CSF rhinorrhea or CSF otorrhea. It occurs whenever there is a mucosal, bony, and dural defect. These defects could lead to communication between the nasal cavity, the paranasal sinuses, or the middle ear cavity and the subarachnoid space. Idiopathic intracranial hypertension (IIH), obesity, obstructive sleep apnea (OSA), and malignancies are well-known conditions that contribute to the development of a CSF leak (1). In this article, we review the pathophysiology of each etiology.

Keywords: Cerebrospinal fluid leak, cerebrospinal fluid otorrhea, cerebrospinal fluid rhinorrhea, encephalocele, endoscopic sinus surgery, idiopathic intracranial hypertension, meningocele, pseudotumor cerebri

How to cite this article:
Alromaih SR. Pathophysiology of skull base defects and cerebrospinal fluid leak. Saudi J Otorhinolaryngol Head Neck Surg 2021;23:91-4

How to cite this URL:
Alromaih SR. Pathophysiology of skull base defects and cerebrospinal fluid leak. Saudi J Otorhinolaryngol Head Neck Surg [serial online] 2021 [cited 2022 Jan 24];23:91-4. Available from: https://www.sjohns.org/text.asp?2021/23/3/91/327572

Introduction

Cerebrospinal fluid (CSF) leak is a rare pathology with many etiologies. It can be spontaneous, congenital, iatrogenic, or traumatic [Figure 1]. A skull base defect may occur along the anterior or lateral skull base manifesting as CSF rhinorrhea or CSF otorrhea. It occurs whenever there is a mucosal, bony, and dural defect. These defects could lead to communication between the nasal cavity, the paranasal sinuses, or the middle ear cavity and the subarachnoid space. Idiopathic intracranial hypertension (IIH), obesity, obstructive sleep apnea (OSA), and malignancies are well-known conditions that contribute to the development of a CSF leak.^[1] In this article, we review the pathophysiology of each etiology.

Figure 1: Etiologies of cerebrospinal fluid leaks

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Spontaneous Cerebrospinal Fluid Leak

Spontaneous CSF leak is a distinct entity in which there is no inciting event. That excludes delayed traumatic CSF leaks, congenital malformations, and defects caused by tumors. There is a strong association between spontaneous CSF leaks and IIH; many patients have clinical and radiological features of IIH. Accurately defining CSF leaks with IIH is crucial for successful management of these patients. This explains the significantly lower success rate of endoscopic repair in these patients in comparison to the overall high success rate of repair of other etiologies.^[2]

Idiopathic Intracranial Hyper tension

IIH is defined as elevated intracranial pressure (ICP) >20 cm H₂O (with an average ranging between 24 cm H₂O and 26.5 cm H₂O) with normal brain parenchyma and without ventriculomegaly or other identifiable causes. IIH is also known by other names, such as benign intracranial hypertension, pseudotumor cerebri, and meningeal hydrops. Normal ICP should not exceed 15 cm H₂O.^{[3],[4],[5],[6]}

The IIH incidence is estimated to be 0.9/10,000 and the prevalence is estimated to be 8.6/100,000 in the general population. Moreover, 80% of IIH patients are females of childbearing age and 90% are obese. The annual incidence increases 20-fold among obese or overweight female patients. The incidence of IIH may also be increasing as the incidence of obesity increases worldwide.^[3],[5]

Patients usually present with vague symptoms, such as intermittent severe headache, tinnitus, or visual disturbances and papilledema, and it may lead to blindness if left unrecognized and untreated.^[5]

The exact cause of IIH is still unknown. However, some mechanisms have been hypothesized about the impaired hydrodynamics of CSF. Researchers believe that cerebral venous hypertension and altered venous outflow are the main mechanisms in the development of IIH. Cerebral venous hypertension and altered venous outflow lead to dysfunctional arachnoid granulations and impaired CSF absorption causing elevated ICP [Figure 2]. As stenotic transverse sinus can be observed in up to 90% of IIH cases, some researchers believe that it could lead to impaired venous outflow. However, given that it is common in the general population and given the possible reversal of a previously stenosed transverse sinus through CSF diversion procedures, one should consider that it could be a consequence of elevated ICP rather than a cause. Thus, the pathophysiology of cerebral venous hypertension is still controversial.^[3],[5]

Figure 2: Proposed pathogenesis of cerebrospinal fluid leak due to elevated intracranial pressure

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Elevated ICP with its dural pulsations can exert direct pressure over the skull base causing bone thinning and resorption. Then, thin areas of the skull base could completely erode, especially in cases of hyperpneumatization with subsequent brain herniation and CSF leak.^[4],[6]

Obesity and Obstructive Sleep Apnea

There is a well-recognized association between body mass index (BMI) and IIH. More than 70% of IIH patients are obese, and weight loss is well known to improve symptoms of elevated ICP and CSF opening pressures. The depth of olfactory fossa and BMI is significantly higher in female patients with spontaneous CSF leaks. This could be explained by increased abdominal pressure and thoracic pressure and the resultant increase in central venous pressure. However, hormonal etiology and increased estrogenicity may also have a role as IIH is more common in females and those with gynecoid lower body obesity.^[3],[7]

OSA is more prevalent in patients with spontaneous CSF leak in comparison to other CSF leak patients and the general population. Even in individuals that do not have chronic IIH, OSA has been associated with recurrent transient spikes of increased ICP. Given the strong association between spontaneous CSF leak due to IIH and OSA, many studies have suggested the need to screen all patients with spontaneous CSF leak for symptoms of both IIH and OSA. This association has been reported in many retrospective studies. However, the association is confounded by heterogeneous patient data, as shown in one meta-analysis; thus, prospective controlled studies are needed to further elaborate this relationship.^[8],[9],[10]

Skull Base and Dural Thickness

The dura membrane is an important structure that protects the entire central nervous system. In a postmortem study, age and female gender had a negative correlation with dural thickness. In other retrospective studies, the thickness of the skull base was found to be greater in patients with traumatic CSF leaks and normal control subjects than in patients with spontaneous CSF, especially in the ethmoid roof, lateral lamella, and anterior face of the sella. Moreover, there is a significant correlation between the thickness of anterior and lateral skull base in patients with spontaneous CSF rhinorrhea. In spontaneous CSF otorrhea, a thin tegmen is significantly associated with lower success rates and a thick tegmen may decrease recurrence after reconstruction. However, whether this thinning in the dura and skull base is a predisposing factor or a consequence of IIH is still controversial.^{[11],[12],[13],[14]}

Skull Base Defects

The lateral recess of the sphenoid sinus and the cribriform plate of the ethmoid bone are the most common sites of meningoceles and spontaneous CSF leaks. The lateral craniopharyngeal canal, known as Sternberg's canal, is a bony congenital defect in the lateral aspect of the sphenoid sinus that may persist into adulthood. It may become a site of spontaneous CSF leaks and/or meningocele, especially with extensive pneumatization of the lateral sphenoid recess coupled with elevated ICP.^[15],[16]

Other locations in the sphenoid sinus have been reported as well. Simmonds and Scott reported a defect along the medial wall of the V2 canal.^[17] Hannabass and Justice reported another case of CSF leak from the optic canal.^[18] In another case report of spontaneous CSF rhinorrhea in a patient with metastatic lung cancer involving the sella, the leak started after 1 week of systemic erlotinib chemotherapy and it was found due to a dural and bony defect at the dorsum sellae. Spontaneous CSF leak from a clival defect through prepontine cistern is a very rare entity; there are only a few case reports in the literature.^{[17],[18],[19],[20],[21]}

Multiple simultaneous skull base defects can exist. Schmitt et al. reported the sixth case of simultaneous anterior and lateral skull base defect causing a CSF leak.^[22] In another retrospective chart review to determine the presence of multiple simultaneous defects among patients with spontaneous CSF rhinorrhea who underwent endoscopic repair, 8 out of 44 patients (18%) were found to have multiple skull base defects.^[22],[23]

A defect in the middle cranial fossa can expose the dura to the middle ear through the tegmen, causing spontaneous CSF otorrhea and/or encephalocele. It may present as hearing loss, blocked ear, or clear otorrhea, and it presents challenges in diagnosis and management because it may mimic serous otitis media. Other locations are exceedingly rare, with only 15 cases of Fallopian canal ^{More Details} meningoceles reported so far. They are difficult to manage with a higher rate of recurrence and facial nerve injury.^[24],[25]

Congenital Cerebrospinal Fluid Leak

Congenital meningoencephalocele may present as an intranasal/extranasal mass. It transilluminates, expands with crying (Furstenberg sign), and may infrequently cause CSF leak. Brain tissue and the meninges could herniate through a defect in the anterior cranial fossa, typically a patent fonticulus frontalis or foramen cecum due to incomplete closure of the anterior neuropore. High index of suspicion should be made with all intranasal midline masses in children, and a biopsy must be avoided until further imaging is carried out and intracranial connection is excluded.^[26],[27]

Iatrogenic Cerebrospinal Fluid Leak

In the current practice, rhinology is the most litigated subspecialty of otolaryngology, and the most common litigated rhinology procedure is functional endoscopic sinus surgery. The most frequently injured site is the lateral lamella of the cribriform plate where the bone is the thinnest part of the anterior skull base. The posterior fovea ethmoidalis and the posterior aspect of the frontal recess are other common sites of iatrogenic injuries.^[28],[29]

Septoplasty and turbinoplasty are relatively safe procedures, with a reported incidence of complications ranging from 5% to 60%; most of these complications are considered to be minor. However, CSF leak has been reported in the literature in case reports and case series. One case report of CSF leak was also reported after inferior turbinate submucosal diathermy.^{[30],[31],[32]}

CSF rhinorrhea could occur after a variety of neurosurgical procedures as well. A dural defect could be created during the procedure, but not adequately repaired. This involves any surgery from the frontal sinus to the clivus. The CSF leak rates after endoscopic skull base surgery vary between centers according to the surgeons' experience and the available multidisciplinary support for such cases. In the largest series from the University of Pittsburgh, the overall rate of postoperative CSF leak was 15.9%.^[29],[33]

Traumatic Noniatrogenic Cerebrospinal Fluid Leak

Dural tears and CSF leaks occur in 10%–30% of skull base fractures because the dura is extremely adherent to the skull base. Moreover, 2.6% of all closed head traumas have CSF leaks from the anterior skull base, but more would have minor leaks that could be occult and heal spontaneously without being noticed. CSF leak due to anterior skull base trauma is 5–6 times more common than lateral and posterior skull base trauma. Following traumatic brain injury, the most common sites of fracture and CSF leak are the frontal sinus (30.8%), sphenoid sinus (11.4%–30.8%), ethmoid roof (15.4%–19.1%), cribriform plate (7.7%), frontoethmoid (7.7%), and sphenoethmoid (7.7%).

Traumatic CSF leak usually presents within 48 h of trauma in more than 50% of cases, and 60%–70% of those cases heal spontaneously. Delayed leak is defined as a leak presenting at least 1 week after trauma. Nearly all delayed leaks manifest within 3 months of trauma. Delayed leak could be due to resorption of a blood clot or separation of the dura from the arachnoid once cerebral edema resolves.^[29]

Conclusion

CSF leak is a rare pathology with many etiologies. It can be spontaneous, congenital, iatrogenic, or traumatic. A skull base defect may occur along the anterior or lateral skull base manifesting as CSF rhinorrhea or CSF otorrhea, and multiple defects could happen simultaneously in the same patient. These defects could lead to communication between the sinonasal or the middle ear spaces and the subarachnoid space, causing clear rhinorrhea or otorrhea, respectively. Knowing the pathophysiology of different entities should help the treating team in managing patients with appropriate investigations, medications, and surgical interventions, to prevent potential complications and to ensure successful repair.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Konuthula N, Khan MN, Del Signore A, Govindaraj S, Shrivastava R, Iloreta AM. A systematic review of secondary cerebrospinal fluid leaks. Am J Rhinol Allergy 2017;31:48-56.
2.	Wang EW, Vandergrift WA 3^rd, Schlosser RJ. Spontaneous CSF leaks. Otolaryngol Clin North Am 2011;44:845-56.
3.	Hoffmann J, Goadsby PJ. Update on intracranial hypertension and hypotension. Curr Opin Neurol 2013;26:240-7.
4.	Martínez-Capoccioni G, Serramito-García R, Martín-Bailón M, García-Allut A, Martín-Martín C. Spontaneous cerebrospinal fluid leaks in the anterior skull base secondary to idiopathic intracranial hypertension. Eur Arch Otorhinolaryngol 2017;274:2175-81.
5.	Stevens SM, Rizk HG, Golnik K, Andaluz N, Samy RN, Meyer TA, et al. Idiopathic intracranial hypertension: Contemporary review and implications for the otolaryngologist. Laryngoscope 2018;128:248-56.
6.	Soler ZM, Schlosser RJ. Spontaneous cerebrospinal fluid leak and management of intracranial pressure. Adv Otorhinolaryngol 2013;74:92-103.
7.	Ito CJ, Reyes-Gelves C, Perry C, Kountakis SE. Body mass index and olfactory fossa depth in patients with and without spontaneous cerebrospinal fluid leaks. ORL J Otorhinolaryngol Relat Spec 2017;79:331-5.
8.	Rabbani CC, Saltagi MZ, Manchanda SK, Yates CW, Nelson RF. Prevalence of Obstructive Sleep Apnea (OSA) in Spontaneous Cerebrospinal Fluid (CSF) Leaks: A prospective cohort study. Otol Neurotol 2018;39:e475-80.
9.	Fleischman GM, Ambrose EC, Rawal RB, Huang BY, Ebert CS Jr., Rodriguez KD, et al. Obstructive sleep apnea in patients undergoing endoscopic surgical repair of cerebrospinal fluid rhinorrhea. Laryngoscope 2014;124:2645-50.
10.	Bakhsheshian J, Hwang MS, Friedman M. Association between obstructive sleep apnea and spontaneous cerebrospinal fluid leaks: A systematic review and meta-analysis. JAMA Otolaryngol Head Neck Surg 2015;141:733-8.
11.	Fam MD, Potash A, Potash M, Robinson R, Karnell L, O'Brien E, et al. Skull base dural thickness and relationship to demographic features: A postmortem study and literature review. J Neurol Surg B Skull Base 2018;79:614-20.
12.	Psaltis AJ, Overton LJ, Thomas WW 3^rd, Fox NF, Banks CA, Schlosser RJ. Differences in skull base thickness in patients with spontaneous cerebrospinal fluid leaks. Am J Rhinol Allergy 2014;28:e73-9.
13.	O'Connell BP, Stevens SM, Xiao CC, Meyer TA, Schlosser RJ. Lateral skull base attenuation in patients with anterior cranial fossa spontaneous cerebrospinal fluid leaks. Otolaryngol Head Neck Surg 2016;154:1138-44.
14.	Stevens SM, Rizk HG, McIlwain WR, Lambert PR, Meyer TA. Association between lateral skull base thickness and surgical outcomes in spontaneous CSF Otorrhea. Otolaryngol Head Neck Surg 2016;154:707-14.
15.	Melo NA, Borges BB, Magliarelli Filho PA, Godoy MD, Pereira LV, Pinna Fde R, et al. Lateral sphenoid sinus recess cerebrospinal fluid leak: A case series. Eur Arch Otorhinolaryngol 2014;271:2587-94.
16.	Tomaszewska M, Brożek-Mądry E, Krzeski A. Spontaneous sphenoid sinus cerebrospinal fluid leak and meningoencephalocele – Are they due to patent Sternberg's canal? Wideochir Inne Tech Maloinwazyjne 2015;10:347-58.
17.	Simmonds JC, Scott AR. Spontaneous CSF rhinorrhea from the trigeminal canal in an adolescent. Int J Pediatr Otorhinolaryngol 2017;98:162-5.
18.	Hannabass K, Justice JM. Spontaneous cerebrospinal fluid leak from the optic canal. SAGE Open Med Case Rep 2017;5:1-3.
19.	Priddy B, Hardesty DA, Beer-Furlan A, Otto B, Prevedello DM. Cerebrospinal fluid leak rhinorrhea after systemic erlotinib chemotherapy for metastatic lung cancer: A familiar problem from an unfamiliar culprit. World Neurosurg 2017;108:992.e11-992.e14.
20.	Oleś K, Składzien J, Betlej M, Chrzan R, Mika J. Spontaneous cerebrospinal fluid leak at the clivus. Wideochir Inne Tech Maloinwazyjne 2016;10:593-9.
21.	Tandon V, Garg K, Suri A, Garg A. Clival defect causing primary spontaneous rhinorrhea. Asian J Neurosurg 2017;12:328-30. [PUBMED] [Full text]
22.	Schmitt B, Badet JM, Chobaut JC, Tavernier L. Double skull base defects with primary spontaneous cerebrospinal fluid leaks in a single patient: Temporal and sphenoid bones. Skull Base 2010;20:455-8.
23.	Lieberman SM, Chen S, Jethanamest D, Casiano RR. Spontaneous CSF rhinorrhea: Prevalence of multiple simultaneous skull base defects. Am J Rhinol Allergy 2015;29:77-81.
24.	Rao N, Redleaf M. Spontaneous middle cranial fossa cerebrospinal fluid otorrhea in adults. Laryngoscope 2016;126:464-8.
25.	Dey JK, Van Gompel JJ, Lane JI, Carlson ML. Fallopian canal meningocele with spontaneous cerebrospinal fluid otorrhea: Case report and systematic review of the literature. World Neurosurg 2019;122:e285-90.
26.	Marfatia HK, Parelkar KA, Chakraborty A, Mishra S. Pediatric meningoencephaloceles endoscopic endonasal repair: Our experience. Allergy Rhinol (Providence) 2018;9:1-6.
27.	Keshri AK, Shah SR, Patadia SD, Sahu RN, Behari S. Transnasal endoscopic repair of pediatric meningoencephalocele. J Pediatr Neurosci 2016;11:42-5. [PUBMED] [Full text]
28.	Tolisano AM, Justin GA, Ruhl DS, Cable BB. Rhinology and medical malpractice: An update of the medicolegal landscape of the last ten years. Laryngoscope 2016;126:14-9.
29.	Gray ST, Wu AW. Pathophysiology of iatrogenic and traumatic skull base injury. Adv Otorhinolaryngol 2013;74:12-23.
30.	Venkatesan NN, Mattox DE, Del Gaudio JM. Cerebrospinal fluid leaks following septoplasty. Ear Nose Throat J 2014;93:E43-6.
31.	Youssef A, Ahmed S, Ibrahim AA, Daniel M, Abdelfattah HM, Morsi H. Traumatic cerebrospinal fluid leakage following septorhinoplasty. Arch Plast Surg 2018;45:379-83.
32.	Abobotain AH, Ajlan A, Alsaleh S. Cerebrospinal fluid leakage after turbinate submucosal diathermy: An unusual complication. Ann Saudi Med 2018;38:143-7.
33.	Kassam AB, Prevedello DM, Carrau RL, Snyderman CH, Thomas A, Gardner P, et al. Endoscopic endonasal skull base surgery: Analysis of complications in the authors' initial 800 patients. J Neurosurg 2011;114:1544-68.