Introduction
Idiopathic intracranial hypertension (IIH) is a syndrome of headache characterized by raised intracranial pressure (or cerebrospinal fluid [CSF] pressure) in the absence of an intracranial mass or hydrocephalus. Clinical exam is almost always normal except for occasional cranial nerve VI palsy and papilledema.[1 ] Papilledema is the hallmark of IIH. Papilledema can be bilateral, asymmetrical, or even unilateral; though it can be absent in some cases. To the best of our knowledge, there are very few cases in literature in which patient presented with CSF rhinorrhoea as an isolated symptom. In this case series, we describe two cases which presented solely with spontaneous rhinorrhoea.
Cases
Case 1
A 38-year-old female presented with acute onset of spontaneous CSF rhinorrhoea, which started a month ago. The patient disregarded the symptom and related it to rhinosinusitis. However, she again had episodes of intermittent nasal discharge on left side. She denied history of headache, vomiting, blurring, visual disturbance, or head injury. The ophthalmoscopic examination revealed papilledema [Figure 1 ] with normal visual acuity and field charting. The laboratory analysis of nasal discharge tested positive for beta-2 transferrin. The magnetic resonance imaging (MRI) cisternography was requested to demonstrate site of leakage. The patient was advised to get MRI on the day of active nasal discharge. The MRI was acquired in prone position with a dry cotton pledget placed in the left nasal opening. A tiny focus of CSF leakage was identified in the left cribriform plate [[Figure 2 ]A; zoomed up [Figure 2 ]D], which was seen continuing posteroinferiorly into the nasal cavity [Figure 2 ]B. The dry cotton pledget got soaked with CSF and appeared hyperintense on T2 weighted images [Figure 2 ]C. In addition, MRI demonstrated perioptic CSF distension [Figure 3 ]A, vertical tortuosity of the optic nerves [Figure 3 ]B and [Figure 3 ]C, empty sella [Figure 4 ]A, and very prominent CSF distended bilateral Meckel’s cave [Figure 4 ]B. No intracranial mass was noted. Moreover, MR venography showed bilateral distal transverse sinus stenosis [Figure 5 ]. Imaging diagnosis of IIH was suggested.
Figure 1: Ophthalmoscopic exam in case 1 demonstrated bilateral optic disc edema. (white arrows)
Figure 2 (A-D): Coronal T2 fat saturated images in case 1 demonstrate a small site of leakage in the left cribriform plate (red arrow; image A) with a small track of fluid extending posteriorly and interiorly (red arrow; image B). A dry cotton pledget was placed at the left nasal opening which got soaked with fluid, appearing T2 hyperintense (image C; white arrow). Image D is a zoomed image a demonstrating site of leakage
Figure 3 (A-C): Coronal T2 weighted images in case 1 through the orbits demonstrates CSF distension of the bilateral perioptic subarachnoid space (white arrows; image A). Oblique sagittal T2 weighted images are showing vertical tortuosity of bilateral optic nerves (red arrows; images B and C)
Figure 4 (A and B): Sagittal and coronal T2 weighted images in case 1 demonstrating empty sella (image A; red arrow) and prominent CSF distended bilateral Meckel's cave (image B; white arrows)
Figure 5: MR venogram axial Maximum Intensity Projection (MIP) image from case 1 demonstrates severe stenosis of bilateral distal transverse sinuses with non opacification of left sigmoid sinus and jugular bulb (red arrows)
Lumbar puncture was performed 2 weeks later at the time of absence of CSF rhinorrhoea, which demonstrated increased opening pressure of 30 cm of H2 O (normal 10–18 cm of H2 O) with normal CSF composition on laboratory analysis. This confirmed imaging diagnosis of IIH. The patient was offered computerized tomography (CT) scan, which she denied. The patient was treated medically and was offered endoscopic surgical repair. Eventually, patient was lost to follow-up.
Case 2
A 55-year-old female presented with sudden onset of copious spontaneous CSF rhinorrhoea, which started 3 weeks ago noted on the right side. She denied history of headache, vomiting, blurring, visual disturbance, or head injury. The ophthalmoscopic examination revealed normal fundus exam, visual acuity, and field charting. The laboratory analysis of nasal discharge tested positive for CSF. The MRI cisternography was requested. The MRI was acquired in prone position. A moderate sized focus of CSF leakage was identified in the right cribriform plate [Figure 6 ]A, which was seen continuing posteroinferiorly into moderate amount of CSF in the right ethmoid air cells [Figure 6 ]B. The MRI also demonstrated a ballooned empty sella [Figure 7 ]A, perioptic CSF distension [Figure 7 ]B, and vertical tortuosity of the optic nerves [Figure 7 ]C,[Figure 7 ]D. No intracranial mass was noted. Imaging diagnosis of IIH was suggested. CT scan showed a corresponding defect in the right cribriform plate [Figure 8 ]. The patient was referred for endoscopic/neurosurgical surgical repair. Surgery confirmed the site of leakage noted on MRI/CT and was repaired with fascia lata patch.
Figure 6 (A and B): Coronal T2 weighted images in case 2 demonstrate a moderate sized leakage of CSF at the level of right anterior cribriform plate (red arrow; image A). Moderate amount of CSF is seen accumulating in the right ethmoid air cells (white arrow; image B)
Figure 7 (A-D): Sagittal T2 weighted image in case 2 demonstrates ballooned empty sella (red arrow; image A). Coronal T2 image shows CSF distended bilateral perioptic subarachnoid space (red arrows; image B). Oblique sagittal T2 weighted images show vertical tortuosity of bilateral optic nerves (white arrows; images C and D)
Figure 8: Coronal high resolution CT scan in case 2 demonstrates a defect in right cribriform plate (red arrow)
Discussion
IIH is not an uncommon clinical condition, primarily affects young obese women with estimated incidence in this population of 19 per 100,000. This is 20-fold higher than in normal-weight individuals.[2 ],[3 ],[4 ] The typical presentation is headache, pulsatile tinnitus, dizziness, nausea, vomiting, visual disturbance, papilledema, and elevated CSF pressures, with symptoms and signs often not always present together and varying with time.[5 ] CSF rhinorrhoea is a rare complication of benign intracranial hypertension with cribriform plate being the most frequent site of CSF fistula formation, followed by the sella turcica.[6 ]
To the best of our knowledge, there are very few cases in the literature with IIH patients solely presenting as CSF rhinorrhoea. Saifudheen et al . (2010) described one case confirmed on MRI and increased CSF opening pressure.[7 ] Rosenfeld et al . (2013) described 4 cases of spontaneous CSF leakage, with one patient having CSF rhinorrhoea as a presenting symptom.[8 ] Perez et al . (2013) described one case with isolated CSF rhinorrhoea.[9 ] Both our cases presenting with sudden onset isolated spontaneous CSF rhinorrhoea.
Epidemiology
The incidence of IIH is 1–2 in 100,000 population but increases to 19 in 100000 young obese women of reproductive age.[2 ],[3 ],[4 ] There is a female predilection over men ranging from 3:1 to 15:1 in the literature.[2 ],[3 ],[10 ] IIH may also occur in children, but association with obesity, and female sex is less common in prepubertal children.[11 ]
Pathophysiology
Although recognized as a clinical entity for more than 100 years now, the pathogenesis of IIH remains unclear. Several mechanisms have been proposed, such as parenchymal edema, increased cerebral blood volume, excessive CSF production, venous outflow obstruction, compromised CSF resorption, and contribution of inflammatory factors.[12 ],[13 ] Despite numerous theories, there is no consensus about the exact cause of IIH.
Says and Joynt reported microscopic evidence of intracellular and extracellular edema,[14 ] which was later supported by MRI.[15 ] Dandy first hypothesized increase in either cerebral blood volume or amount of CSF in IIH.[16 ] An excessive CSF production and abnormally increased outflow resistance to the CSF has also been proposed.[10 ],[12 ],[17 ]
The most important risk factors of IIH are obesity and female gender with majority of men with IIH are also obese.[18 ] There is a positive correlation between body mass index and the risk of IIH.[19 ] Successfully treated IIH with increased weight was found to be associated with the recurrence of this disease.[20 ] The severity of obesity correlated with more advanced clinical symptomatology, which significantly reduced even with a small weight reduction.[21 ],[22 ]
Despite a stronger risk factor, it remains undetermined how obesity causes IIH. Few suggestions include increased intra-abdominal pressure probably leading to reduced cerebral venous drainage and chronic inflammation associated with obesity causing pro-thrombotic and pro-inflammatory state abnormal metabolism of vitamin A.[10 ],[13 ],[23 ],[24 ],[25 ]
Sex hormones have also been attributed to IIH because of the preferential occurrence among post-pubertal, pre-menopausal women with no gender predilection before puberty.[18 ],[26 ] IIH has been linked to use of oral contraceptive pills and polycystic ovarian syndrome (PCOS). There is a high prevalence of PCOS in women referred for IIH ranging from 39-57%.[27 ],[28 ]
Recent study by Skau et al . evaluated the natriuretic peptide system as a possible cause of altered intracranial pressure autoregulation in patients with IIH.[29 ] Several drugs such as retinoids and steroids have been shown to induce Aquaporin (AQP) 1 expression suggesting the causative role of AQP1 in the pathogenesis of drug-induced IIH.[30 ],[31 ]
Recently, there have been reports that some patients with IIH have bilateral transverse sinus stenosis (BTSS).[32 ] This lead to a debate on whether such a stenosis is the cause or effect of IIH.[33 ] Venous sinus stenting was, therefore, used in some patients with conflicting results.[33 ],[34 ],[35 ],[36 ],[37 ] Another important observation was that one-third of the patients with BTSS had normal CSF pressure, suggesting that BTSS is only one of the contributing factors causing IIH.[38 ]
Clinical presentation
Majority of the times IIH presents as headache, papilledema, visual symptoms and signs, without any lateralizing findings in the neurological examination, and normal CSF findings.[39 ] The headache in IIH should be progressive with at least one of these characteristics; daily occurrence, diffuse and/or constant (non-pulsating), and aggravated by coughing or straining.[40 ] Infrequently, IIH may present in the absence of papilledema.[41 ]
The diagnostic criteria of IIH were first defined by Dandy in 1937[16 ] and were later modified as “Modified Dandy Criteria” by Smith in 1985.[42 ] The current modified Dandy criteria used for the diagnosis are (i) signs and symptoms of increased intracranial pressure; (ii) no other neurological abnormalities or impaired level of consciousness; (iii) elevated CSF opening pressure with normal CSF composition; (iv) a neuroimaging study that shows no etiology for increased intracranial pressure; and (v) no other cause for intracranial hypertension found.[43 ]
Imaging
MRI or contrast-enhanced CT are the imaging that can be performed for typical IIH patients.[44 ]
Friedman et al . proposed updated criteria for the diagnosis which required:[45 ]
Papilledema, normal neurologic examination except for intracranial nerve abnormalitiesNeuroimaging findings including normal brain parenchymaNormal CSF composition and elevated lumbar puncture openingIn the absence of papilledema, the diagnosis would be suggested with at least 3 of the following neuroimaging features were present additionally:
Empty sellaFlattening of the posterior aspect of the globeDistention of the perioptic subarachnoid space with or without a tortuous optic nerve.Transverse venous sinus stenosis.
Additional MRI findings that have been seen in IIH are flattening of posterior sclera and intraocular protrusion of the prelaminar optic nerve [Figure 9 ]A and [Figure 9 ]B.[46 ]
Figure 9 (A and B): Axial MRI images demonstrate flattening of posterior sclera in known patients with IIH (image A; yellow arrows) and intraocular protrusion of the prelaminar optic nerves (image B, red arrows)
Both high-resolution noncontrast CT and MR cisternography have been utilized for the diagnosis of a CSF leak. The sensitivity, specificity, and accuracy of CT cisternography were 92%, 100%, and 93%, respectively compared to 87%, 100%, and 89%, respectively for MR cisternography. In addition, CT and MR cisternography complement each other, with CT demonstrating the bone defect and MR demonstrating CSF leak leading to combined sensitivity, specificity, and accuracy improving to 95%, 100%, and 96%, respectively.[47 ]
Conclusion
Spontaneous CSF rhinorrhoea is a known complication of IIH, however, sole presenting symptom in IIH is extremely rare. IIH typically presents with headache, pulsatile tinnitus, dizziness, nausea, vomiting, and visual disturbance. In the absence of trauma, MR cisternography along with MRI brain should be offered to the patients to identify the site of leakage as well as changes of IIH. These include empty sella, distended perioptic subarachnoid space, vertical tortuosity of the optic nerves, flattening of posterior sclera, and intraocular protrusion of the prelaminar optic nerve. In addition, MR venography may be performed to exclude bilateral venous sinus stenosis.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
