Background and purpose To assess the role of MR venography (MRV) for detecting transverse sinus stenosis, to determine the importance of this finding in idiopathic intracranial hypertension (IIH), and to propose an index that contributes to this diagnosis.
Materials and methods We retrospectively assessed consecutive intracranial MRV of patients aged >18 years diagnosed with IIH according to the diagnostic criteria, between January 2010 and July 2012. The assessments were randomly analyzed by three radiologists. Stenoses in the right and left transverse sinuses were independently classified according to the following scale: 0, normal; 1, stenosis <33%; 2, stenosis 33–66%; 3, stenosis >66%; and 4, hypoplasia or agenesis. We established an index based on multiplication of the stenosis scale values for each transverse sinus. A point and range estimate of the sensitivity, specificity, and the area under the receiver operating characteristic curve was performed to obtain cut-off points to differentiate between controls and patients.
Results 63 individuals were included in this study: 32 (50.8%) diagnosed with IIH (31 (96.9%) women and 1 (3.1%) man) and 31 (49.2%) controls. According to all of the examiners, the IIH group showed a higher degree of stenosis than the control group. Index values ≥4 for a diagnosis of IIH had a sensitivity and specificity of 94.7% and 93.5%, respectively.
Conclusions MRV should be used to assess patients with suspected IIH, and bilateral transverse sinus stenosis should be considered for the diagnosis. The stenosis classifying index proposed here is a fast and accessible method for diagnosing IIH.
- Intracranial Pressure
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Idiopathic intracranial hypertension (IIH) is characterized by increased CSF pressure without a definite structural cause.1 ,2 While the exact physiopathogenesis remains unknown, an increase in intracranial venous pressure, which may result from stenosis of the venous sinus, has been proposed.3–5
IIH is more common in women of reproductive age, and obesity is an important risk factor. The incidence in the general population is estimated to be 0.9 cases/100 000 people, but can reach 19.3/100 000 in young and obese women.6 ,7
Headache, which is the main symptom of IIH, is experienced by most patients.8 Vision loss may occur at the onset or during the development of the disease; the onset is often insidious and, in some cases, asymptomatic,9 which reinforces the importance of early IIH diagnosis.
Historically, imaging tests were primarily used to rule out a specific cause for an increase in intracranial pressure or conditions that mimic clinical signs of pseudotumor cerebri, such as venous thrombosis.8 Presently, MRI is used routinely because it can detect indirect signs that indicate clinical intracranial hypertension or even signs specifically associated with IIH. The main signs include an empty sella turcica; rectification of the posterior wall of the eyeball with or without optic nerve protrusion on the surface of the papilla; tortuosity and enhancement of the optic nerve, and distention of its perioptic subarachnoid space; and slit-like ventricles. These findings present in highly variable ways, with a broad range of sensitivities and specificities described in the literature.10 ,11
MR venography (MRV) can also detect transverse sinus stenosis, which may be present in up to 90% of IIH patients.12 Although this finding has been widely reported over the past decade, few studies have proposed a specific scale to define its sensitivity and specificity. Furthermore, correcting the stenosis should be considered for managing these patients because this may normalize intracranial pressure.3 ,10 ,13 ,14
Our study aimed to assess the role of MRV in detecting transverse sinus stenosis, to determine the importance of this finding in IIH diagnosis, and to propose an index that differentiates these patients from healthy individuals.
Materials and methods
The research ethics committee of our institution approved this study. We retrospectively reviewed consecutive series of intracranial MRV of patients aged >18 years who were followed up at the IIH department of our institution between January 2010 and July 2012. Patients were included only if they met the diagnostic criteria for IIH established in the literature,2 as follows: signs and symptoms of a generalized increase in intracranial pressure or papilledema; a proven increase in intracranial pressure measured in the lateral recumbent position (opening pressure at lumbar puncture >25 cm H2O); normal CSF composition and absence of hydrocephalus, vascular, or structural damage on image analysis; and absence of other identifiable causes of intracranial hypertension. We excluded patients who had undergone surgery involving lumboperitoneal derivation and with suspected venous sinus thrombosis. We reviewed the medical records of patients included in the study to assess the presence of headache, papilledema, and visual impairment throughout the clinical course of the disease and to obtain the pressure at lumbar puncture to assess its association with diagnosis time, body mass index (BMI), visual impairment, and the proposed index. The ratio between BMI (which was calculated by using height and weight obtained at the time of MRV) and the proposed index was also evaluated.
Age and sex matched controls were selected after reviewing the consecutive cranial MRI and MRV of patients aged >18 years without a history of diseases that could increase intracranial pressure or symptoms that would indicate IIH or suspicion of venous abnormality; the MRV was obtained only to complement the brain scans in these cases. Patients with normal results were included in the control group.
MRVs were performed using a 1.5 T Sonata MC (Siemens, Ehrlund, Germany) and an eight channel MRI coil with a T1 weighted, three-dimensional gradient echo sequence with the following technical parameters: TE=1.7; TR=5.03; FOV=250; thickness 1.1 mm; NEX=1; flip angle=20°. All examinations were performed with gadolinium paramagnetic contrast at a dose of 0.4 mL/kg with a maximum of 20 mL. The images were obtained on the sagittal plane before (mask) and after administering the contrast agent, with subsequent subtraction and three-dimensional reconstruction using maximum intensity projection.
Three radiologists with at least 6 years of experience in neuroradiology randomly analyzed the images. The radiologists underwent brief individual training with example cases of patients diagnosed with IIH with bilateral transverse sinus stenosis; these cases were not included in the study. The examiners assessed the MRV acquisition sequence and its three-dimensional reconstructions on a workstation by using a region of interest. The examiners did not know whether the test belonged to a patient with IIH or to a control because they were blinded to the patients' clinical information.
The examiners measured and classified focal stenosis of the right and left transverse sinuses separately by comparison with the immediate pre-stenosis segment (table 1, figure 1). Hypoplasia was considered when the full length of the transverse sinus diameter was less than one-third of the superior sagittal sinus.
The index proposed in this study was termed the index of transverse sinus stenosis (ITSS). This index consisted of the product of the numbers of the stenosis scale for each transverse sinus, according to the following formula:
The product, rather than the sum, of the scale was used because the MRV of patients with IIH shows bilateral stenosis,12 ,14 and re-establishing the flow on only one side normalizes intracranial pressure.13 Likewise, unilateral hypoplasia of the transverse sinus is considered a normal variant and does not increase intracranial pressure.15 Thus an individual should be considered normal if the diameter of at least one of the transverse sinuses lacks stenosis. Using the sum of the degree of stenosis instead of the product for the proposed index in these cases could result in an intermediate value and a false positive.
A statistician performed all statistical analyses. The means and SDs were calculated for the quantitative variables (age and CSF pressure). The qualitative variables (presence of headache, papilledema, and visual impairment) were analyzed by calculating the absolute and relative frequencies (percentage).
Inferential analyses were performed to confirm or refute evidence found in the descriptive analysis by using Pearson's χ2 test, Fisher's exact test, and the Mann–Whitney U test.
The Shapiro–Wilk test revealed absence of normality of the variables. Spearman's rank correlation coefficient was used to assess the association between CSF pressure at lumbar puncture (cm H2O) and diagnosis time (months), BMI (kg/m2), and ITSS, as well as the association between BMI (kg/m2) and ITSS.
The weighted κ was computed to evaluate the inter-rater agreement among the three examiners regarding the ordinal stenosis score. Because multiple raters were involved, the κ value reported here is the appropriately weighted average of the individual κ values. The details of this calculation are described here: http://www.stata.com/manuals13/rkappa.pdf. A point and range estimate of sensitivity, specificity, and area under the receiver operating curve (ROC) was performed to obtain cut-off points to distinguish between patients and controls.
The adopted significance level (α) was 5%, and all statistical analyses were performed using Stata V.12.
This study included 63 individuals: 32 (50.8%) diagnosed with IIH and 31 (49.2%) controls. The patients were diagnosed with IIH at different times; some were undergoing pharmacological treatment with the recommendation to lose weight. The clinical profiles of these individuals are shown in table 2.
The control group included 29 (93.5%) women and 2 (6.5%) men, with a mean age of 32.4 years (range 20–52 years; SD 10.1 years). The IIH group included 31 (96.9%) women and 1 (3.1%) man; mean age was 34.4 years (range 19–58 years; SD 12.3 years). Mean CSF pressure at lumbar puncture measured in this group was 40.5 cm H2O (range 17–92 cm H2O; SD 20.0 cm H2O). Papilledema, headache, and visual impairment were present in 27 (84.4%), 28 (87.5%), and 25 (78.1%) patients, respectively. CSF pressure and the presence of papilledema, headache, and visual impairment were only assessed in the IIH group.
The degree of stenosis in the right and left transverse sinuses was assessed individually. Regarding the degree of stenosis, the combined concordances among the three examiners were as follows: 0.5674 (z=13.29, p<0.001) for the right transverse sinus and 0.5679 for the left transverse sinus (z=14.70, p<0.001). By classifying the level of concordance (via the κ coefficient with linear weighting), as suggested by Altman,16 we observed moderate concordance among the examiners for both sinuses. In the inferential results, the IIH group showed a greater degree of stenosis than the control group for all examiners in both transverse sinuses. Unilateral stenosis >33% was found in 7 subjects (22.5%) in the control group. Nine (28%) of the 32 patients included in this study underwent conventional venous angiography and stenting of the transverse sinus following performance of MRV, at which time stenosis was confirmed.
The ITSS was analyzed to establish a potential value to distinguish controls from patients using information from the ROC; the three ROC areas with each respective 95% CI, sensitivity, and specificity for the best cut-off value are presented in table 3.
A formal statistical test for determining equality of two or more ROC areas is available in STATA V.12 (command roccomp). According to this test, the three ROC areas were not statistically significantly different (χ2(2)=1.99, p=0.3691). However, this formal test does not return evidence regarding cut-offs and their specificity and sensitivity in a global way. Because we observed moderate inter-rater agreement and a lack of significant difference between the three ROC areas, we combined all ratings from all three radiologists to provide a single ROC analysis with a single sensitivity and specificity (test sample size, 63×3 (189 assessments)). Moreover, although it is not formal, such an approach might be helpful for inferentially determining a cut-off point for all assessed tests and not just per examiner. Based on this analysis, an ITSS of 4 was a satisfactory cut-off value because it classified 94.18% of patients and controls accurately, in convergence with separated ratings. The sensitivity and specificity for the highest correctly classified percentages of the ITSS for each individual examiner, and as a whole, are summarized in table 3. No subject in the control group had an index >4, but 10 (31%) patients in the IIH group had an index ≤4.
Finally, the following factors were investigated only in the IIH group: the associations between CSF pressure at lumbar puncture (cm H2O) and diagnosis time (months), BMI (kg/m2), visual impairment, and ITSS (by the three examiners), and the association between BMI (kg/m2) and ITSS (by the three examiners).
The inferential results revealed that CSF pressure was not related to BMI (r=0.013, p=0.944), visual impairment (p=0.395), or ITSS (examiner 1, r=0.144, p=0.431; examiner 2, r=−0.202, p=0.262; and examiner 3, r=−0.041, p=0.825). CSF pressure was related to diagnosis time—that is, the pressure tended to be lower when more time had elapsed since the diagnosis (r=−0.398, p=0.024). BMI was not related to ITSS, as assessed by examiner 1 (r=0.130, p=0.477), examiner 2 (r=0.019, p=0.916), and examiner 3 (r=−0.011, p=0.953).
The epidemiological data in our study were consistent with the IIH literature, with a greater number of women of reproductive age comprising the IIH group.1 ,2 Further, the prevalence of headache and papilledema among the patients in this study (87.5% and 84.4%, respectively) were similar to the reported values.17–19 However, our values were closer to the lower limits, which may be because we included patients who were undergoing treatment.
In our study, the diagnosis of >33% bilateral transverse sinus stenosis in patients with IIH varied between 87.5% and 96.8%, depending on the examiner. These data are consistent with the literature,3 ,12 supporting the importance of these findings in the IIH diagnosis. Previously, this finding was interpreted as an anatomical variation or flow artifact associated with the time of flight sequence. However, many studies have since confirmed a focal reduction in the diameter of the transverse sinus through the use of computerized angiotomography, digital venography, and other highly accurate angiography sequences that utilize contrast medium.3 ,12 ,13 The diagnostic criteria, which were revised in 2013,20 point to transverse sinus stenosis as one of the neuroimaging findings that indicates pseudotumor cerebri syndrome in the absence of papilledema, and in association with normal neurologic examination and CSF composition, and elevated lumbar puncture opening pressure.
The classification proposed by Farb et al,12 which includes a score that represents the degree of stenosis of each transverse sinus, showed high sensitivity and specificity for the diagnosis of IIH. In our study, we used a transverse sinus diameter reduction scale, in which the examiners assessed one-third increment increases, in order to classify the stenosis by using a fast and practical method. We postulated that this classification method would have better reproducibility. Because reproducibility was dependent on different learning curves between examiners with prior individual training in stenosis classification, and considering that the concordance for all three examiners was calculated in combination and not separately, we deemed the concordance between the observers as satisfactory.
Anatomical variations that reduce the diameter of only one transverse sinus may be present in up to 30% of individuals with normal intracranial pressure,15 which may lead to a false positive diagnosis. However, the ITSS involves multiplying the stenosis scale for each transverse sinus. Therefore, we offer a method that may improve the diagnosis of bilateral stenosis and reduce the occurrence of false positives in individuals with normal intracranial pressures and unilateral transverse sinus stenosis because the zero degree of the normal transverse sinus cancels out the ITSS value.
ITSS values ≥4 had a sensitivity of 94.7% and a specificity of 93.5% for the diagnosis of IIH. Similar to Farb et al,12 we found no linear association between ITSS and mean pressure at lumbar puncture or BMI, which may be explained by variations in the distribution of collateral veins. Thus although ITSS was effective for diagnosing or excluding IIH, it is not recommended for categorizing severity.
Ophthalmologic monitoring in IIH generally assesses visual loss,21 which may be initially asymptomatic with subsequent rapid development.22 In our study, all types of visual impairment were assessed, ranging from an episode of blurred vision or scotomata to vision loss. Riggeal et al14 observed no correlation between the degree of transverse sinus stenosis and clinical manifestations, including visual impairment. Consistent with this observation, we found no significant association between visual impairment and a high ITSS value, which is an additional indicator of the inability of this index to assess IIH severity. However, the fact that transverse sinus stenosis is present, even in cases with few clinical manifestations, reinforces the importance of early diagnosis to prevent progression to irreversible vision loss.
Nine (28%) of the 32 patients included in this study posteriorly underwent conventional venous angiography and stenting of the transverse sinus, with confirmation of the stenosis. All of these patients had clinical improvement and reduced lumbar puncture pressure after angioplasty.
Our study had several limitations. First, we sampled patients who were diagnosed at different times and were undergoing different IIH treatments. Our sample included recently diagnosed, untreated patients and patients who were undergoing clinical treatment, causing fluctuations in the pressure levels at lumbar puncture. The lumbar puncture pressure levels tended to be lower in patients who had been diagnosed previously, which was likely due to these patients having undergone treatment. Furthermore, the use of ITSS is limited by normal variations in transverse sinus anatomy. The retrospective nature of this study was a limitation when comparing the presence of transverse sinus stenosis with the pressure value at lumbar puncture because these assessments were not performed on the same day. However, such an assessment would have had limited value in our study because of its invasive nature as well as the rapid variations in pressure values even shortly after lumbar puncture.23
In three patients with bilateral transverse sinus stenosis and ITSS ≥4, CSF pressure was <25 cm H2O at lumbar puncture when the measurement was performed close to the MRV date, presumably because patients were undergoing treatment. These patients had several previous lumbar punctures with pressure >25 cm H2O and met the standard criteria for IIH. This may have indicated residual transverse sinus stenosis in these patients, even with pressure levels that were considered normal. This interesting finding has a precedent in the literature in a study by Bono et al.24 However, this finding is not consistent with the report of Lee et al,25 which described a case with complete resolution of ‘venous obstruction’, but only when the CSF pressure was reduced to 8 cm H2O. The assumption that transverse sinus stenosis causes the increase in intracranial pressure, in combination with limitations in venous returns due to weight gain, is strengthened by reports describing good outcome following reversion of stenosis via angioplasty in patients who did not respond to clinical treatment.13 ,26 ,27 This technique results in clinical improvement and normalizes intracranial pressure, which may occur immediately after angioplasty.28
It remains unknown whether transverse sinus stenosis is a cause or consequence of the increased intracranial pressure. Some authors suggest that both components exist.14 ,29 Studies have shown persistence26 or resolution25 ,30 of transverse sinus stenosis after intracranial pressure is reduced to normal levels. Moreover, the higher prevalence of stenosis in patients with IIH indicates that this finding is relevant for diagnosis as well as management, since stenting is performed in some cases.
We propose that MRV be included in the assessment of patients suspected of having IIH, especially when the clinical findings are inconclusive, and that bilateral transverse sinus stenosis be considered to support the diagnosis combined with clinical and other radiological parameters. The ITSS proposed in this study to classify stenosis is a fast and accessible method for helping to predict which patients are most likely to have IIH, and it could be used in future prospective studies.
The authors acknowledge scientific support from Fundação Instituto de Pesquisa e Estudo de Diagnóstico por Imagem (FIDI).
Abstract in Portuguese
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
- Abstract in Portuguese - Online abstract
Contributors GBdSC: project development, data collection, and manuscript writing. SLdAM: project development. MHI, LATT, RSdC, and MLSS: data collection. APJ and HC-M: statistical analysis and manuscript writing. NA: project development and manuscript writing.
Competing interests None declared.
Ethics approval This study was approved by Universidade Federal de São Paulo Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.
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