Association of ocular findings and outcome in cerebral venous thrombosis.

BACKGROUND: Cerebral venous thrombosis (CVT) is a potentially life-threatening underdiagnosed disease. Headache is a common but nonspecific finding in CVT. Other features such as ocular finding can assist to correct diagnosis, but their frequency in CVT has not been previously evaluated. The aim of this study is to evaluate the ocular symptoms and signs in CVT and their association with outcome.
METHODS: The demographic, clinical, laboratory, radiological, and outcome data were collected and analyzed from patients referred to a tertiary hospital during 6 years. Based on delay from symptom onset to hospital admission, mode of onset was categorized as acute (<2 days), subacute (2-14 days), or chronic (>14 days).
RESULTS: Fifty-three patients were identified with a mean age of 33.7 years (17-60 years). Ocular symptoms and signs were the most frequent clinical presentations (77.4%) following headache (83%). Papilledema and diplopia were the main findings in chronic CVTs (P = 0.003 and 0.002, respectively). Proptosis was significantly associated with thrombosis in cavernous sinus (P = 0.00). Otherwise, there was no relationship between any specific ocular findings and the type or number of thrombosed sinus or hemorrhagic infarction. Mortality rate and recurrence in our patients were 3.8% and 5.7%. Absence of proptosis and vision loss was associated with favorable outcome (P = 0.001 and 0.003, respectively).
CONCLUSION: Ocular features were among the most common presentation of CVT in every three phases of CVT and could be the sole finding of CVT. Patients who do not have vision loss and proptosis might have a better outcome in CVT.

Introduction

Cerebral venous thrombosis (CVT) is a rare and potentially life-threatening disease. It is believed to be an underdiagnosed condition which usually affects young and middle-aged population.[123] The clinical picture of CVT is highly variable and can mimic several neuro-ophthalmologic conditions. Outcome of CVT may vary from complete recovery to serious neurological deficits or death.[45]

While ocular presentation seems to be common in CVT barring few case reports, no detailed account of ocular manifestations in CVT exists in literature. On the other hand, prompt diagnosis regarding visual symptoms and signs and early treatment of patients with CVT significantly improve the outcome of the disorder, especially in severe cases.[67] Therefore, the current study was conducted to find ocular characteristic of CVT patients and their association with number and type of thrombosed cerebral veins and outcome.

Methods

The study was performed at a tertiary referral general hospital that serves patients from all over the country. Data from demographic characteristics, clinical symptoms and signs, particularly ocular features, medical and drug history, laboratory results (including tests of procoagulatory states), cerebrospinal fluid (CSF) pressure, neuroimaging findings, and outcome of the patients, were collected. Patient's data from July 2004 to November 2010 were extracted from the medical records which were kept in the registry system of the hospital. Patients were followed up for a period of at least 1 year since the time of admission to the hospital. The diagnosis of CVT was confirmed by two neurologists and a radiologist. All patients had an initial brain computed tomography (CT) scan and magnetic resonance imaging/venography (MRI/MRV) and/or conventional angiography. In the absence of MRI/MRV or any discrepancy between the clinicians and radiologist regarding the diagnosis of CVT, that case was excluded from the study. Based on the time from symptom onset to hospital admission, mode of onset was categorized as acute (<2 days), subacute (2–14 days), or chronic (>14 days).[8] CSF pressure more than 180 mmH2O was considered as raised intracranial pressure (ICP).[9] All patients with diagnosis of cerebral venous sinus thrombosis were treated according to the standard protocol and received anticoagulant (AC) in the form of dose adjusted intravenous unfractionated heparin with an at least doubled activated partial thromboplastin time.

Patients signed written informed consent. When they were not available, we called the patients or their family by phone and permissions for data acquisition were achieved. Ethical Committee of both hospital and vice chancellor of research of the university approved the protocol of the study. Data analysis was performed using SPSS 16 (SPSS Inc., Illinois, USA). Values with normal distribution were analyzed with Chi-square and t-test. Otherwise, Mann–Whitney test was used. The level of significance was P < 0.05.

Results

Fifty-three patients (40 females and 13 males) were recognized with the diagnosis of CVT. Mean age was 33.7 years with a range from 17 to 60 years (standard deviation: 11.7) and female to male ratio of 3.07.

Headache was the most frequent clinical finding of CVT among the patients (n = 44, 83%). Ocular findings in studied patients were quite common and were present in 77.4% of them (n = 40). Papilledema was the most frequent ocular feature (n = 36, 68%) and was bilateral or asymmetric. Sixth nerve palsy was present in 16 patients and was unilateral in 7 (43.7%). Ocular characteristics of our patients and other clinical features are summarized in Table 1.

Table 1

Symptoms and signs in patients with cerebral venous thrombosis

The most frequent cause of CVT in patients was their underlying disease (n = 21, 40%), which consisted of infectious disease (7), autoimmune disorders (5), pregnancy and puerperium complications (4), malignancy (3), and hematologic disorders (2). Other identified causes included procoagulatory states (n = 16, 30%), oral contraceptive pill (n = 15, 28%), and in vitro fertilization (IVF) hormonal drugs (n = 3, 5.6%) and other drugs (n = 6, 11%). 32% of patients (n = 17) had more than one contributing factors for CVT, and 17% of them (n = 9) had no identifiable cause (idiopathic) in spite of extensive workup.

The involved cerebral sinus in patients with CVT diagnosis in order of decreasing frequency included left transverse (n = 28,53%), right transverse (n = 23,43.3%), superior sagittal (n = 16, 30%), jugular (n = 13, 24.5%), deep cerebral veins including straight and galen (n = 8, 15%), and cavernous sinus (n = 6, 11.3%). 58.4% of patients (n = 31) presented with two or more thrombosed cerebral sinuses. Three patients had thrombosis in five cerebral veins. Simultaneous thrombosis was occurred mostly in sagittal-transverse and jugular-transverse veins in 15 and 13 patients, respectively. Cavernous sinus was the only cerebral vein which accompanied no involvement of other sinuses.

As shown in Table 2, diplopia and papilledema were late presenting features in CVT, unlike other ocular presentations which did not differ significantly in acute, subacute, and chronic stages. Eighty percent of patients had high CSF pressure which was significantly associated with bilateral papilledema (P = 0.04).

Table 2

Association of ocular findings and onset of clinical presentation of CVT

There was no significant association between ocular features and involvement of a specific type of cerebral venous sinus, number of thrombosed cerebral veins, or the presence of hemorrhagic infarct on initial brain CT scan. The only exception in association of the type of involved cerebral sinuses and a specific ocular finding was proptosis. Four of our patients presented proptosis, and all of them had cavernous sinus thrombosis (P = 0.00).

Mortality rate and recurrence in our patients were 3.8% and 5.7%, respectively. No death occurred in CVT patients who had no ocular features. Absence of vision loss and proptosis in patients with CVT was significantly associated with favorable outcome [Table 3]. From 34 patients who did not have any complaint of vision loss, 32 patients improved finally (94%). However, the rate of improvement was 60% and 73% in patients with unilateral and bilateral vision loss, respectively. The association of other ocular findings and outcome of patients with CVT is given in Table 3. Although not statically significant, all patients who did not have papilledema improved and no recurrences were seen.

Table 3

Association of ocular finding on outcome of patients with cerebral venous thrombosis

Discussion

Our study of 53 patients showed that ocular findings were among common presentations of CVT. These findings could be detected in every three stages of the disease (acute, subacute, and chronic) with complete ophthalmologic examination. Diplopia and papilledema had been significantly presented in late stages. In spite of the fact that papilledema was a common finding in CVT (nearly in 70% of patients) and a good indicator of raised ICP in these patients, its absence in early stages could not rule out the diagnosis of CVT. However, significant presentation of diplopia and papilledema in chronic CVTs shows that these patients may not go to the emergency department. Because of chronic state of symptoms, they may seek ophthalmology clinics. Considering proper neuroimaging including brain MRI with and without contrast and brain MRV could help correct diagnosis of CVT and rule out space-occupying lesions.

The mortality rate in our patients was 3.8% which was lower than the results of International Study on Cerebral Vein and Dural Sinus Thrombosis (4.3%)[10] and other series in our region (7.8%–14.5%).[11] This could be due to therapeutic protocol in our patients that all of them had received AC. Among controversies regarding AC in the treatment of CVT, the current evidence shows that anticoagulation is safe and all CVT patients without contraindication should be treated with AC. Concomitant hemorrhage related to CVT is not a contraindication for AC in these patients.[121314] Improvement in radiological investigation and identification of less severe cases are another factors that probably contributed to low rate of mortality.[15]

Two patients who died were 29-year-old and 24-year-old females. Both had bilateral sixth nerve palsy, papilledema, and vision loss. The first patient had undergone IVF previously and had hemorrhagic infarct and thrombosis in the left transverse sinus and jugular vein on neuroimaging. Then, she developed generalized tonic–clonic seizure, hemiparesis, and loss of consciousness and her condition deteriorated. The second was a case of hepatitis B who presented with headache, proptosis, and multiple cranial nerve palsies. She had normal CSF analysis and cavernous sinus thrombosis. In previous studies, papilledema, altered level of consciousness, coma, intracerebral hemorrhage, diagnostic delay, and septic CVT were predictors of poor outcome.[1617] In our study, vision loss and proptosis were associated with lower rate of improvement. Moreover, CVT patients with no papilledema showed good outcome as all of them improved with no recurrence.

As limitation of the study, data on clinical features and laboratory findings of some patients were collected retrospectively, and sometimes, enough information could not be extracted from their medical documents.

Conclusion

Our study showed that ocular presentations were common in patients with CVT. Proptosis was significantly associated with cavernous sinus thrombosis. Otherwise, involvement of a specific cerebral sinus was not associated with the type of ocular features. The absence of proptosis and vision loss was associated with favorable outcome in CVT. Although not statically significant, the absence of papilledema also could be a good indicator of CVT prognosis. Regarding the frequent prevalence of ocular findings in CVT patients resulted from this study and the association of outcome with some of them, ophthalmologists should have necessary knowledge about CVT and its ocular symptoms and signs.

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Conflicts of interest

There are no conflicts of interest.