Abstract
Background/objectives
To compare the yield of magnetic resonance venography (MRV)/computed tomography venography (CTV) in a group of overweight women with incidentally-discovered papilledema and symptomatic intracranial hypertension (IC-HTN) patients without risk factors for dural venous sinus thrombosis (DVST).
Design
Retrospective cohort study.
Methods
Retrospective cohort study of female patients between ages 16 and 50 with papilledema, body mass index >25 kg/m2 and MRV/CTV imaging. Patients were excluded if they had risk factors for DVST. The incidence of DVST and clinical features were retrieved. Patients were divided into those with incidentally-discovered papilledema (Group-1) and those who presented due to symptoms of IC-HTN (Group-2).
Results
One hundred three patients (45 Group-1, 58 Group-2) were included in the study. Group-2 patients were more likely to have pulsatile tinnitus (p = 0.017), transient visual obscurations, and showed a trend towards increased headache (p = 0.058). Group-2 was also more likely to have been treated with acetazolamide (p < 0.01) and undergo lumbar puncture (p = 0.02). DVST was initially reported in four patients (one in Group-1, three in Group-2), but after further review, two cases (one from Group-1, one from Group-2) were found to be false positives. The final two DVST diagnoses were in Group-2 and presented with significant neurological symptoms.
Conclusions
DVST was not found among a group of 45 young, overweight women with incidentally-discovered papilledema and without DVST risk factors. We therefore believe it is reasonable practice to perform MRI alone, without dedicated MRV/CTV, in the investigation of young, overweight women with incidentally-discovered papilledema without risk factors for DVST.
Subject terms: Magnetic resonance imaging, Physical examination
Introduction
Papilledema, or optic disc oedema as a result of raised intracranial pressure, may be caused by various intracranial pathologies including mass lesions, meningeal processes, or dural venous sinus thrombosis (DVST) [1]. When papilledema is suspected, investigations such as magnetic resonance imaging (MRI), magnetic resonance venography (MRV) or computed tomography venography (CTV), and a lumbar puncture are usually performed to determine the underlying cause [1]. A common cause of papilledema among patients seen by neuro-ophthalmologists is idiopathic intracranial hypertension (IIH), which occurs predominantly in young, obese women. It is diagnosed based on the Modified Dandy Criteria, which requires the presence of signs and symptoms of intracranial hypertension (IC-HTN), absence of localising neurologic signs, normal neuroimaging, normal constituents of cerebrospinal fluid (CSF) on lumbar puncture, and no secondary cause to IC-HTN [2]. Even though it is not required for diagnosis of IIH in ‘typical’ (young obese women) patients, MRV or CTV is commonly performed in patients with papilledema to rule out DVST, which represents 0.5–1% of all strokes [3]. DVST creates an obstruction of the dural sinus, leading to increased venous pressure which may result in significant neurological symptoms such as severe headache, seizures, encephalopathy or focal syndromes that require prompt medical attention [4]. Patients with DVST may also present only with IC-HTN [5].
Although MRV and CTV are routinely performed to rule out DVST in anyone with papilledema, the value of these tests in patients who are young, female, obese and fit a typical IIH presentation is still debated [6]. Moreover, many patients may be seen in clinic after they have only had an MRI of the brain. The argument against routinely performing these tests in patients typical for IIH is the low yield of the tests and additional costs involved. Proponents of routinely obtained venous imaging argue that the consequences of missing a case of DVST outweigh the potential costs. Previous studies have aimed to address the tests’ value but were limited in their sample size or in the population that was studied. For example, some studies included patients regardless of gender, body habitus, medical history, or presence of risk factors for venous sinus thrombosis such as male sex, non-obesity, post-surgery status, use of oral contraceptives, deep vein thrombosis, and hypercoagulable states [7–9].
Thus, it remains debatable whether venous sinus thrombosis should be routinely ruled out with MRV or CTV in young, obese women with a typical IIH profile who lack risk factors for DVST [6]. The purpose of this study was to compare the utility of MRV or CTV in young, overweight women with incidentally-discovered papilledema compared to patients presenting with symptoms of IC-HTN and papilledema.
Methods
Research ethics board approval was obtained by the University of Toronto Research Ethics Board. Data were collected using a retrospective patient record review of consecutive patients who presented with papilledema to tertiary neuro-ophthalmology clinics in Toronto, Ontario, Canada. Consecutive female patients were enrolled in this study if they met the following inclusion criteria: (i) age 16–50 years, (ii) papilledema determined by fellowship-trained neuro-ophthalmologists, (iii) Optical coherence tomography (OCT)—retinal nerve fibre layer (RNFL) thickness >100 μm in at least one eye, (iv) body mass index >25 kg/m2, (v) available MRV/CTV head imaging obtained to evaluate cause of papilledema. A definition of overweight was used rather than obesity to be more inclusive given the potential for discrepancies between self-reported and actual weight. Patients were excluded if they had risk factors for DVST, including personal or family history of venous thrombosis, connective tissue disease/rheumatological disease, cancer, significant head trauma, pregnancy, or past neurosurgical or recent surgical treatment (within 3 months). The following information was collected for all patients: age at presentation, presence of symptoms (headache, pulsatile tinnitus, transient visual obscuration, and diplopia), treatment at presentation, OCT-RNFL thickness, mean deviation from Humphrey 24-2 SITA-Fast visual field testing, type of imaging obtained (MRV/CTV), lumbar puncture results (opening pressure and CSF cytology) and final diagnosis. Weight was based on patient self-report, which has been shown to correlate reasonably well with actual weight [10]. MRV was further classified into time-of-flight, phase contrast, or gadolinium-enhanced technique. IIH was diagnosed according to the modified Dandy criteria [11] and presumed IIH was diagnosed when lumbar puncture was deferred but all other criteria for IIH were met.
Included patients were divided into two groups according to the reason for clinical presentation. Group-1 included patients with incidentally-discovered papilledema, meaning that they presented to an eye care provider for a reason unrelated to the IC-HTN such as new refraction, routine exam, or unrelated eye complaint. Group-2 included patients who sought medical attention for a symptom related to IC-HTN, such as new headache, blurred vision, pulsatile tinnitus, or diplopia related to a sixth nerve palsy.
Statistical analysis was performed using SPSS (IBM, 2019). Mean and standard deviation (SD) were reported for variables analysed. Comparisons between Group-1 and Group-2 were performed using chi-square and Student’s t tests with Bonferonni correction. Statistical significance was accepted for p values < 0.05.
Results
A total of 103 patients (mean age 30.4, SD = 9.0) were included in the study. Group-1 consisted of 45 patients and Group-2 contained 58 patients. Baseline characteristics of the patients are shown (Table 1). Group-2 patients were significantly more likely to have pulsatile tinnitus (p = 0.017), transient visual obscuration (p = 0.007) and showed a trend for increasing headache compared to Group-1 (p = 0.058) (Fig. 1). Group-2 patients were also more likely to be treated with acetazolamide at the time of presentation (p = 0.0007). There was no difference in age, BMI, OCT-RNFL thickness or mean deviation between groups. Lumbar puncture was more likely to be performed in Group-2 patients (36 vs. 15 patients, p = 0.02), and Group-2 patients had a higher mean lumbar puncture opening pressure (38.5 vs. 33.0, p = 0.013). Most patients (86; 83.5%) had 3D gadolinium-enhanced MRV, whereas five patients (4.8%) had 2-dimensional time-of-flight MRV, three patients (2.9%) had phase-contrast MRV, and nine patients (8.7%) had CTV. A congenital hypoplastic transverse sinus was found in 12 patients (n = 5 in Group-1, n = 7 in Group-2) and distal transverse sinus stenosis was found on at least one side in 100/103 (96%) of patients. Final diagnoses included IIH or presumed IIH (n = 94), drug-induced IC-HTN (n = 4; all in Group-1), DVST (n = 2; both in Group-2), intracranial mass (n = 1 in Group-1, n = 1 in Group-2) and POEMS (n = 1; Group-1). Both intracranial masses were meningiomas with the patient in Group-1 having a small meningioma compressing the torcula and the patient in Group-2 having a large petrous apex meningioma.
Table 1.
Patient characteristics. Bolded p values represent statistically significant results.
| Group-1 | Group-2 | p | |
|---|---|---|---|
| n | 45 | 58 | |
| Mean age (±SD) | 30.5 ± 10.3 | 30.2 ± 7.8 | 0.89 |
| BMI (kg/m2) | 34.8 ± 6.4 | 34.4 ± 5.6 | 0.68 |
| Treated with acetazolamide at presentation | 5 (11%) | 24 (41%) | 0.0007 |
| Unilateral papilledema | 3 (6.7%) | 5 (8.6%) | 0.73 |
| OCT-RNFL avg thickness (μm) | 178.6 ± 72.8 | 186.6 ± 92.1 | 0.29 |
| Humphrey mean deviation | −3.26 ± 4.7 | −3.82 ± 4.6 | 0.40 |
| Lumbar puncture available | 15 | 36 | 0.02 |
Fig. 1. Presenting symptoms in patients in Group-1 vs. Group-2.
Numbers above bars represent number of patients having specified symptom. p values represent comparisons between groups.
DVST was initially reported to be found in 4 patients (n = 1 in Group-1 and n = 3 in Group-2). All four patients had emergency evaluation and two patients (one from Group-1 and one from Group-2) were determined to have had a false positive result after subsequent CTV and further review of the MRV with expert neuro-radiologists, respectively. A final diagnosis of DVST was confirmed in two patients. Both had a BMI greater than 30 kg/m2, had bilateral papilledema, and no brain parenchymal abnormality on MRI. Both presented with new significant neurological symptoms. The first patient presented with severe right-sided headache (rated 10/10 in intensity), nausea, vomiting, and double vision. The second patient presented with severe headache, neck pain, nausea, vomiting, and double vision. The thrombosis was found to be in the right transverse and sigmoid sinuses and internal jugular vein in patient 1 using 2D time-of-flight MRV and in superior sagittal, torcula and right transverse-sigmoid sinuses in patient 2 using 3D gadolinium-enhanced MRV.
Discussion
In our cohort of young, overweight female patients with papilledema without risk factors for DVST, only 2 out of 103 (1.9%) had a final diagnosis of DVST. Both patients were in the group of patients that sought medical attention due to symptoms of DVST (Group-2) and no patient with incidentally-discovered papilledema was ultimately found to have DVST (Group-1). Both patients diagnosed with DVST had significant new neurological symptoms at presentation including severe headache, nausea and vomiting, and diplopia. In young, overweight patients presenting with new neurological symptoms suggestive of IC-HTN with papilledema, we found that MRV/CTV needed to be performed in 29 patients to find 1 case of DVST. No patient with incidentally-discovered papilledema was found to have DVST and there was a higher likelihood of a false positive result in this patient group. This suggests that there is room for clinical judgement when deciding to perform imaging to rule out DVST in this patient group with incidentally-discovered papilledema.
Previous published smaller studies have found similar results to the current report. Lee and Brazis [8] prospectively recruited 22 young, female, overweight patients with a typical IIH phenotype and no patient was found to have DVST. Purvin et al. [12] studied 20 patients with IC-HTN related to impaired cerebral drainage of which ten patients had DVST. All ten DVST patients sought medical attention due to sudden onset severe headache and nine patients had marked papilledema. The authors concluded that the abrupt onset and marked severity of symptoms in patients with thrombosis should help in differentiating them from those with IIH. Taken together, these small studies suggested that patients with IC-HTN related to DVST have a more severe phenotype compared to those with IIH.
Additional studies found a larger proportion of DVST in patients presenting with IC-HTN. Agarwal et al. [7] included 308 patients with IC-HTN and found that DVST was present in 35 individuals (11%). However, this study did not stratify patients based on risk factors for DVST since medical conditions such as pregnancy, post-Caesarean section, history of deep vein thrombosis, oral contraceptive use, hyperhomocystenemia and leukaemia were present in the DVST group. Moreover, a large proportion of DVST patients were men (74.3%), which based on their gender alone would not be considered typical for IIH. Lin et al. [9] studied 106 patients (19 men and 87 women) with IC-HTN without mass lesions and found DVST in ten patients (four men and six women) [9]. The cause of DVST in the six women were postsurgical, infectious, related to oral contraceptives, hypercoagulable state, with none identified in one individual. One individual who was severely obese had no identifiable risk factors for thrombosis. Biousse et al. [5] reported 160 consecutive patients with DVST and found that one-third of patients presented with isolated signs of IC-HTN and four patients had papilledema without headache. Over 1/3 of patients were men which is atypical for IIH. Patients were not differentiated by risk factors for IIH such as BMI or DVST risk factors at presentation and severity of their symptoms at presentation was not reported. Moreover, Zhao et al. [13] reported three patients with chronic DVST with decreased vision, bilateral papilledema and the absence of headache. However, all of these patients would have qualified for symptomatic IC-HTN in our group given the presentation of severe vision loss related to papilledema. These above studies demonstrate that DVST should be ruled out in patients with IC-HTN and it is rare, but possible for DVST to present with isolated IC-HTN and potentially minimal symptoms in young obese women.
This is the first study to look at MRV/CTV in a group of patients with incidentally-discovered papilledema, which is a common way for IIH patients to present to ophthalmology clinics with patients often seeing an optometrist for an updated refraction, routine follow-up exam or an unrelated eye complaint and are found to have optic disc oedema. Our study suggests that these patients are distinct in that they rarely harbour sinister causes of increased ICP and the yield of investigating these patients with venography is more likely to yield a false positive result rather than a true thrombosis. This indicates that findings of DVST in this patient group should be reviewed with expert neuro-radiologists or complimentary studies obtained to ensure that the finding is indeed representative of true pathology. Given the extremely low risk for secondary causes of IC-HTN in this group, patients with incidentally found papilledema who already had CT/MRI without venography and who do not have risk factors for DVST can likely be safely observed clinically without the need for an additional venous study.
The strengths of this study include the relatively large sample size of incidentally-discovered papilledema patients and the availability of venography in all patients. Moreover, each patient was seen by a fellowship-trained neuro-ophthalmologist, helping ensure that the optic disc oedema was most consistent with papilledema. Limitations of this study include the absence of a lumbar puncture in some papilledema patients; however, each patient was followed clinically and none of these patients were found to eventually harbour a secondary cause of IC-HTN. Many neuro-ophthalmologists will defer lumbar puncture in patients with a typical history of IIH and only mild optic disc oedema. Moreover, the low incidence of DVST in this study was likely a result of exclusion of patients with known risk factors for this condition and the need for each included patient to be female and overweight. It is theoretically possible that DVST patients with papilledema may not have been referred for neuro-ophthalmological evaluation; however, we believe it is unlikely given the referral patterns in our centres to routinely obtain ophthalmology/neuro-ophthalmology consultation for patients with DVST after diagnosis.
In conclusion, DVST is rare among overweight women with papilledema and without risk factors. No patient with incidentally-discovered papilledema was ultimately diagnosed with DVST and false positive results were more common in this patient group. The group of patients who have incidentally-discovered papilledema seem to be distinct in that they likely do not harbour sinister causes of IC-HTN and the yield of investigating these patients with venography studies is very low. As such, we believe it is reasonable practice to perform MRI/CT head alone, without dedicated MRV/CTV, in the investigation of young, overweight women with incidentally-discovered papilledema without risk factors for DVST.
Summary
What was known before
Magnetic resonance or CTV is routinely obtained in patients with raised intracranial pressure, but its utility in patients with ʻtypical’ idiopathic IC-HTN is debated.
What this study adds
DVST is extremely rare in overweight young women without DVST risk factors and typically presents with significant neurological symptoms. DVST was not found in 45 consecutive young female patients presenting with incidentally-discovered papilledema.
Data availability
The data that support the findings of this study are available on request from the corresponding author, JAM. The data are not publicly available due to their containing information that could compromise the privacy of research participants.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Footnotes
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author, JAM. The data are not publicly available due to their containing information that could compromise the privacy of research participants.