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ORIGINAL ARTICLE
Adv Biomed Res 2017,  6:165

Factors Influencing the Incidence of Papilledema in Patients with Cerebral Venous Thrombosis


Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Date of Web Publication26-Dec-2017

Correspondence Address:
Zahra Pirhaji
Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2277-9175.221464

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  Abstract 


Background: Cerebral venous thrombosis (CVT) is an uncommon cerebrovascular disease with a wide spectrum of symptoms and severity. This study analyzes the factors influencing the incidence of papilledema in patients with cerebral venous thrombosis. Materials and Methods: In this research 65 patients with CVT were examined between 2011 and 2013, and the patients were followed up one, three, six, and twelve months after the initial diagnosis. They were separated into two groups according to presence or absence of papilledema. We analyzed the frequency of symptoms and risk factors of cerebral venous thrombosis and the intensity of papilledema as time passed, as also the frequency of the involved sinus, in two groups of patients with and without papilledema. Results: This study showed that the most common symptom was headache, with a frequency of 92.3% and the least common symptoms were ataxia and quadriparesis, with a frequency of 1.5%. The most common risk factors were high waist circumference (WC) and oral contraceptive pil (OCP) use, and also in patients with papilledema the intensity is reduced as time passes. Conclusion: This investigation showed that there was no significant relation between the frequency of risk factors and symptoms and intensity of papilledema as time passed in the two groups. The results showed that the most common sinuses involved in patients with papilledema were sagittal and lateral sinuses, which included 66.7%, and the most common sinus involved in patients without papilledema, which was the lateral sinus that included 40%.

Keywords: Cerebral venous thrombosis, papilledema, sinus


How to cite this article:
Saadatnia M, Pirhaji Z. Factors Influencing the Incidence of Papilledema in Patients with Cerebral Venous Thrombosis. Adv Biomed Res 2017;6:165

How to cite this URL:
Saadatnia M, Pirhaji Z. Factors Influencing the Incidence of Papilledema in Patients with Cerebral Venous Thrombosis. Adv Biomed Res [serial online] 2017 [cited 2020 Jul 16];6:165. Available from: http://www.advbiores.net/text.asp?2017/6/1/165/221464




  Introduction Top


Cerebral venous thrombosis (CVT) is an uncommon cerebrovascular disease with a wide spectrum of symptoms and severity. The disease can be acute, subacute, or chronic.[1] It affects about five in one million and women are affected three times more than men, usually including young people.[2],[3] The disease is observed in 0.5 to 1% of all cases of stroke.[4] The most common symptoms are headache (70 to 80%), weakness (40 to 54%), hemiparesis (40%), seizures (30%), and papilledema (20 to 30%).[4]

Clinical manifestations of the disease depend on such factors as thrombosis location, age, and the presence or absence of simultaneous brain lesions.[5] The most important risk factors of the disease may include coagulation disorders, concurrent cancer, drug use (especially oral contraceptive drugs).[6],[7] In a study conducted in 2008 by Wasay et al., the disease was detected in 57% of 182 patients with cerebral venous thrombosis, and in 43%, the disease was idiopathic.[8]

Disease manifestations depend on many factors, one of which is the affected area of the brain. In the local cerebral involvement of the brain, hemiparesis and aphasia are considered as the most common symptoms.[9] Another factor causing the manifestation of the symptoms is venous sinus involvement. When the lateral sinus is involved, frequent manifestations of the disease include background disease symptoms, such as, fever, natural symptoms, and discharge from the ear, while in the case of superior sagittal sinus involvement, symptoms such as increased intracranial pressure and papilledema are considered among the most common symptoms.[10],[11] One of the important symptoms of papilledema is vision loss.[12] Magnetic resonance imaging (MRI) or computed tomography scan (CTS) are the first choice for the diagnosis for CVT.[7]

In 25% of the CVT patients the only symptom is headache and no papilledema is seen.[13],[14]

Papilledema is one of the causes of cerebral venous thrombosis and is a condition where the optic nerves become inflamed because of the skull pressing down on them. The most important causes of papilledema can be brain tumors, cerebral edema, meningitis, and cerebral venous thrombosis. However, in some cases there is no known cause for its occurrence. On the other side, in Iran, no study has yet been performed to determine the risk factors. Considering this fact that at least a quarter of patients with cerebral venous thrombosis may have no obvious signs such as papilledema, it makes it difficult to detect CVT. The present study was performed to determine factors affecting the incidence of papilledema in patients with cerebral venous thrombosis.


  Materials and Methods Top


This research is a descriptive–analytical study performed between 2011 and 2013, at Al-Zahra Medical Center in Isfahan, Iran. The population included patients with CVT, diagnosed between 2011 and 2013, and admitted to the center. The inclusion criteria were, the incidence of CVT and the patients' participation agreement to contribute to the study at identified periods.

The sample size required for the study was estimated using the formula for prevalence studies, taking into account the 95% confidence level, the incidence of papilledema in patients with CVT, which was estimated at about 20% in other studies,[5] and accepting a 15% error rate for 30 individuals.

The method started with the initial diagnosis. The patients were examined by ophthalmoscopy and were evaluated for the presence or absence and severity of papilledema.

Mild papilledema: Circumferential halo, elevation of nasal border, no major vessel obscuration.

Moderate papilledema: Circumferential halo, elevation of all borders, obscuration of one or more segments of major blood vessels leaving the disc.

Severe papilledema: Complete halo, elevation of whole nerve head, including the cup, total obscuration on the disc of a segment of a major blood vessel on the disc.[15]

The initial diagnosis also considered the risk factors of cerebral venous thrombosis (blood levels of protein C, protein S, homocysteine, antithrombin 3, factor 5 Leiden, anticardiolipin antibodies (ACLA), antinuclear antibody (ANA), lupus anticoagulant, pregnancy, malignancy, and drugs consumption). These were investigated and the results were recorded in a special questionnaire prepared for this purpose.

The patients were followed up during the first, third, sixth, and twelfth months of treatment for the presence of papilledema, using the ophthalmoscope.

The information was analyzed using the SPSS software version 22, T-test, and Chi-square tests.


  Results Top


In this study, 65 CVT patients with a mean age of 37.6 ± 12.3 years were studied. Among them 30 patients (46.2%) suffered severe papilledema, with 21 mild papilledema (70%), two moderate papilledema (6.7%), a seven severe papilledema (23.3%). The mean ages of patients with and without papilledema were 35.6 ± 12.7 and 39.2 ± 11.9 years, respectively, and according to the t-test, no significant difference was observed between the two groups (P = 0.25). The sex ratio (female/male) in the two groups was 7/23 and 10/25, respectively, and according to the Chi square test, the difference between the two groups was not significant (P = 0.63). [Figure 1] shows the frequency of symptoms in CVT patients. It is clear that the most common symptom is headache with a frequency of 92.3% and the least common symptoms are ataxia and quadriparesis with a frequency of 1.5%. [Figure 1] shows the frequency of symptoms in patients with and without papilledema. The Fisher's exact test and Chi-square test on the data showed that no significant difference was observed between the two groups in terms of the frequency of symptoms in patients with papilledema and patients without papilledema (P > 0.05).
Figure 1: Frequency of symptoms in patients

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Of the 65 CVT cases studied in this research, 28 cases (43.1%) had a metabolic syndrome, 17 cases were non-papilledema, and 11 were papilledema patients (48.6 vs. 36.7%), but according to the Chi square test, no significant difference was observed between the two groups. [Figure 2] shows the frequency of risk factors for CVT patients where the most common risk factors were high WC and OCP use. [Table 1] shows the distribution of the mentioned risk factors for patients with papilledema and patients without papilledema. From the data, both the Fisher's exact and Chi-square test showed that none of the frequency differences of the risk factors in patients with papilledema and patients without papilledema were statistically significant (P > 0.05).
Figure 2: Frequency of risk factors of CVT in patients

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Table 1: Distribution of clinical signs in patients with and without papilledema

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As stated previously, the patients were followed up in the initial diagnosis of CVT, one, three, six, and twelve months later, in terms of progress or regress. The results of the regression of papilledema in the follow-up are shown in [Figure 3]. According to this figure, in patients with papilledema, the intensity is reduced as time passes.
Figure 3: Frequency of papilledema severity up to one year after the incidence

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Average duration of disease in patients with papilledema was 1.82 ± 3 months ranging from zero to twelve months. On the other hand, linear regression analysis of the data showed that none of the studied risk factors had a significant effect on the duration of papilledema. (P > 0.05)

Laboratory findings also indicated that one patient (1.5%) of the papilledema group had a positive ANA test. None of the patients had a positive anti-neutrophil cytoplasmic antibody (ANCA) test. On the other hand, four patients (6.2%) suffered from vasculitis, two of them were papilledema patients, but two were patients without papilledema (6.7 vs. 5.7%), and there was no significant difference between the two groups (P = 0.99).

In [Figure 4], the frequency of the type of involved sinus is shown. On the basis of the above figure, the most common sinuses involved in the studied patients were sagittal and lateral sinuses (frequency = 30). In [Table 2], the frequency distribution of the type of involved sinus based on papilledema and lack of papilledema is shown. Results show that the most common sinus involved in papilledema patients were sagittal and lateral sinuses that included 20 of the 30 patients, equivalent to 66.7%. However, the most common sinus involved in other patients without papilledema is a lateral sinus that included 14 of the 35 or 40% of the patients. The Fisher's exact test on the data shows that the difference in the frequency of the involved sinus, based on the papilledema and lack of it in patients is significant (P = 0.002).
Figure 4: Frequency of the sinus involved in patients

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Table 2: Distribution of the type of sinus involved based on the incidence and lack of papilledema

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  Discussion Top


The overall objective of this study was to determine the factors affecting the incidence of papilledema in patients with cerebral venous thrombosis. In this study from 65 patients under study, 30 patients (46.2%) suffered papilledema, with severe edema in seven patients (23.3%). Other studies have also shown that there is a relationship between the incidence of cerebral vein thrombosis and papilledema. In other words, papilledema is created as a result of increased intracranial pressure and with increased intracranial pressure the pressure is transported to the optic nerve sheath, damaging the axoplasmic transport of the optic nerve. Intra-axonal transport obstruction leads to the swelling of the axons and leak of water, proteins, and other cell contents in the extracellular space of the optic nerve and eventually causes edema in the optic nerve.[14] Christian et al., in a study in 2011, estimated the incidence of papilledema in patients with CVT, as much as 20 to 30%.[4] In 2009, Ferro et al., studied 624 patients with CVT, reporting the outbreak of papilledema in as much as 29%.[6] In the present study, there was no significant difference between the age and sex distribution of the two groups of patients with and without papilledema. The clinical signs observed in CVT patients, in both groups, also showed no significant difference. Notably, headache, papilledema, and hemiparesis were the most common clinical symptoms in these patients and the high incidence of papilledema could also be a clear indication of the relationship between cerebral venous thrombosis and papilledema. Buschi's study, in 2008, also marks papilledema as the third common symptom in patients with CVT. In this study, of the 12 identified risk factors, a high level of WC, oral contraceptive use, and metabolic syndrome, were the most common risk factors of developing CVT in patients. On the other hand, the most common sinuses involved in the patients were the sagittal and lateral sinuses. The most involved sinus in patients without papilledema was the lateral sinus, while the lateral and sagittal sinuses were mostly involved in patients with papilledema. In other studies, when the lateral sinus was involved, the frequent manifestations of the disease included background disease symptoms, such as, fever, natural symptoms, and discharge from the ear, while in case the superior sagittal sinus was involved, symptoms such as increased intracranial pressure and papilledema were considered among the most common symptoms.[10],[11] However, the results showed that the frequency of CVT symptoms in both groups of patients (with papilledema and patients without papilledema) revealed no significant difference between them and from among the risk factors of CVT, only polycythemia was different in the two groups of patients with papilledema and patients without papilledema and the other factors were not significantly different.


  Conclusion Top


The results of this study show that after one year of disease onset, two patients (3.6%) still had mild papilledema and one patient had severe papilledema, but due to the low number of cases with prolonged papilledema, it was impossible to examine the impact of the variables and risk factors of the disease. Therefore, this case was within the limitation of the present CVT study and studying a greater volume of patients with CVT is recommended for future studies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Coutinho JM, Ferro JM, Canhão P, Barinagarrementeria F, Cantú C, Bousser MG, et al. Cerebral venous and sinus thrombosis in women. Stroke 2009;40:2356-61.  Back to cited text no. 2
    
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Stam J. Thrombosis of the cerebral veins and sinuses. N Engl J Med 2005;352:1791-8.  Back to cited text no. 4
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Wasay M, Bakshi R, Bobustuc G, Kojan S, Sheikh Z, Dai A, et al. Cerebral venous thrombosis: Analysis of a multicenter cohort from the united states. J Stroke Cerebrovasc Dis 2008;17:49-54.  Back to cited text no. 8
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Appenzeller S, Zeller CB, Annichino-Bizzachi JM, Costallat LT, Deus-Silva L, Voetsch B, et al. Cerebral venous thrombosis: Influence of risk factors and imaging findings on prognosis. Clin Neurol Neurosurg 2005;107:371-8.  Back to cited text no. 9
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Teichgraeber JF, Per-Lee JH, Turner JS Jr. Lateral sinus thrombosis: A modern perspective. Laryngoscope 1982;92:744-51.  Back to cited text no. 10
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Biousse V, Ameri A, Bousser MG. Isolated intracranial hypertension as the only sign of cerebral venous thrombosis. Neurology 1999;53:1537-42.  Back to cited text no. 11
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Sadun AA, Currie JN, Lessell S. Transient visual obscurations with elevated optic discs. Ann Neurol 1984;16:489-94.  Back to cited text no. 12
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Ferro JM. Causes, predictors of death, and antithrombotic treatment in cerebral venous thrombosis. Clin Adv Hematol Oncol 2006;4:732-3.  Back to cited text no. 13
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Tanislav C, Siekmann R, Sieweke N, Allendörfer J, Pabst W, Kaps M, et al. Cerebral vein thrombosis: Clinical manifestation and diagnosis. BMC Neurol 2011;11:69.  Back to cited text no. 14
    
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Frisen L. Swelling of the optic nerve head: A staging scheme. J Neurol Neurosurg Psychiatry 1982;45:13-8.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]


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