記住我
Click on image for details.
ORIGINAL ARTICLE
Year : 2023 | Volume
: 71
| Issue : 5 | Page : 916-922
Profile and Outcome of Prospective Non-Septic Lateral Sinus Thrombosis Patients from a Stroke Unit of a Developing Country
Abbas M Mirza1, Girish B Kulkarni1, Subasree Ramakrishnan1, Veerendrakumar Mustare1, Ravi Yadav1, Arun K Gupta2
1 Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bengaluru, Karnataka, India
2 Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bengaluru, Karnataka, India
Correspondence Address:
Girish B Kulkarni
Department of Neurology, NIMHANS, Hosur Road, Bangalore - 560 029, Karnataka
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/0028-3886.388114
Background: Due to effective treatment of middle ear infections there is a change in etiologies causing lateral sinus thrombosis (LST) and outcome. There is a paucity of literature describing homogenous group of patients with nonseptic LST (NS-LST).
Objective: To describe the clinical profile, risk factors, outcome of patients of NS-LST seen at a single center from South India.
Methods and Materials: Prospective, observational study of 100 patients of NS-LST patients, diagnosed by magnetic resonance imaging (MRI) seen at the stroke unit.
Results: During 2 years, 100 patients of NS-LST (isolated: combined: 27:73) (male: female: 44:56), mean age: 31.45 ± 11.13 years, were seen. Subacute presentation (74%) with headache, seizures, focal deficits, and features of raised intracranial pressure were presenting features. Hyperhomocysteinemia (61%), anemia (57%), postpartum state (41%), OCP use (37%), and low VitB12 (32%) were commonly seen risk factors. Imaging with MRI compared withcomputerized tomography (CT) had better diagnostic sensitivity (100% vs. 67%), detection of parenchymal (81% vs. 67%)/hemorrhagic (79% vs. 74%) lesions, and cortical vein thrombosis (31% vs. 15.46%). Treatment with anticoagulation and supportive therapy resulted in good outcome (mRS (0-2)) at 3 months in 81%.There were four deaths, all during admission (one – isolated, three – combined) and 11 patients underwent decompressive surgery. Patients with low GCS level of sensoriumat admission, hemiparesis, combined LST, cerebellar involvement, and decompressive craniectomy had a poor outcome.
Conclusion: This single-center large cohort study of NS-LST patients brings out the clinical features, risk factors (peculiar to developing countries), and the superiority of MRI in the diagnosis. Majority of patients have good outcome, with low mortality with 10% requiring decompressive surgery.
Keywords: Anticoagulation, lateral sinus, stroke, thrombosis, venous stroke
Key Message: The profile, management, and outcome of non septic lateral sinus thrombosis (NSLST) patients is different from septic etiology. In this prospective, single center, large cohort of NSLST patients we describe the risk factors, clinical and imaging profile, treatment modalities and note the good outcome in majority of patients.
Cerebral venous thrombosis (CVT) is a rare form of stroke with varied clinical presentations and outcomes, based on the site, the extent of thrombosis, presence of collateral circulation, and subsequent recanalization.[1],[2] It is common in developing countries and younger population.[3] Superior sagittal and lateral sinuses are frequently affected sinuses in CVT. In two-third of patients, multiple sinuses are involved; the most frequent combination being sagittal and lateral sinus.[4] Isolated lateral sinus thrombosis (LST) is less frequent (10%–32%).[4],[5] Due to its close proximity to the middle ear, the septic etiology was common in patients with LST in older literature. With the effective and rational use of antibiotics over the past few decades, the etiological cause of LST has changed.[2],[6] In a large study of 62 isolated LST patients, only one patient had the middle ear infection.[4] The majority of cases of LST are now due to noninfectious causes (nonseptic LST (NS-LST)).The literature on clinical presentation and outcome of NS-LST is limited and especially from developing country where it is more common.[4],[7],[8] The objective of the study was to describe the demographic, clinical, and radiological features, and outcome of a large cohort of prospectively seen NS-LST patients.
Patients and Methods
Study design
It was a prospective, observational cohort study of consecutive patients of NS-LST seen at the Stroke Unit of a Tertiary Care, University Teaching Neurology Hospital of a developing country during January 2012 to December 2013. The patients were followed up for the next 1 year. The study was approved by the institutional ethics committee and an informed consent was taken from either patient or his relative.
Patient selection
The study included patients of ≥18 years, presenting to the emergency services of our institute with headache with/without focal seizures with/without neurological deficits, features of raised intracranial pressure, or encephalopathy. They were clinically evaluated and various diagnoses were considered including CVT. All subjects underwent computerized tomography (CT) scan of brain (plain and contrast) at admission unless contraindicated.We undertook the CT scan of brain followed by MRI for all patients, because CT is easily available at emergency services. Imaging with magnetic resonance imaging (MRI) was planned once the patient is stabilized, co-operative, and planned during working hours. It also gives an opportunity to evaluate and compare these two modalities in our study. The sequences used in MRI were as follows: T1, T2, FLAIR, diffusion, susceptibility weighted, T1 contrast, and MR venogram. The diagnosis of LST was based on the presence of direct signs of CVT on MRI of the brain demonstrating the thrombus, which were as follows: visualization of the thrombus on T1, T2, and FLAIR-weighted images in MRI,[3] the presence of filling defect on T1 contrast images,[3] and nonvisualization of sinus on MR venogram confirmed with any of the above features.[9] The thrombus on MRI brain was divided into three stages: acute, subacute, and chronic stage depending on T1- and T2-weighted images.[9] In patients with isolated LST, thrombosis was limited to sigmoid and transverse sinus, while in the combined sinus thrombosis group, there was additional involvement of the superior sagittal sinus, cortical veins or deep venous sinuses. Exclusion criteria were as follows: age <18 years and CVT secondary to infection, trauma, tumor, and surgery. Ear infection was ruled out by history, local examination, and when in doubt opinion from ear surgeon.
Data collection
At admission history of presenting symptoms, risk factors, and neurological examination findings were noted. Mode of onset was divided into acute(<48 h), subacute (48 h to 30 days), and chronic (duration >30 days).[1] Based on presenting symptoms, patients were categorized into three groups: encephalopathy (progressive decrease in sensorium or altered sensorium in absence of focal deficits), focal neurological deficits with preserved consciousness, and the third group with features of isolated intracranial hypertension (IIH) (a headache with or without sixth nerve palsy and papilledema).[10] Altered sensorium was diagnosed if there is fluctuation in the level of consciousness, reduced alertness, and diminished response to verbal or tactile stimuli.[11] Aphasia was diagnosed in patients with clear sensorium.
Risk factor analysis included complete hemogram, liver and renal function tests, serum Vitamin B12, homocysteine, antinuclear antibody profile, and IgG and IgM antiphospholipid antibodies. Patients were tested for retroviral illness by ELISA after an informed consent. In the present study, anemia was defined as hemoglobin level <13g/dL in men, 12g/dL in nonpregnant women, and 11g/dL in pregnant women.[12] It was classified based on mean corpuscular volume into normocytic (80–100fL), microcytic (<80fL), and macrocytic (>100fL) anemia.[13] Polycythemia is considered when the hemoglobin level is >17g/day (hematocrit >50%) in men and 15g/dL (hematocrit > 45%) in women.[13] The laboratory cut-off values for Vitamin B12 deficiency:<174pg/mL and hyperhomocysteinemia: >15umol/L (micro mol/litre).
Treatment aspects such as anticoagulation, antiedema measures, and complications were noted. In patients undergoing surgery, indications and type of surgery were noted. All patients were treated with unfractionated subcutaneous heparin during the acute phase. Oral anticoagulation with acenocoumarol was continued at discharge with regular PT monitoring to maintain INR between1.5 and 2.[14] The duration of anticoagulation was for 6 months in patients with reversible risk factors (like OCP use and puerperium), and 1 year in idiopathic cases. Patients were taken up for decompressive surgery when there was a deterioration in sensorium and appearance of signs of Uncal/central herniation, with repeat imaging confirming the clinical suspicion and after failure of antiedema measures.
Outcome measurement
In hospital, mortality was noted. All the patients were regularly followed by one of the authors in the outpatient department. The new symptoms were recorded and a detailed neurological examination was done. Functional status was assessed at admission and during follow-up visit at 3months using modified Rankin score,[15],[16] Barthel index for activities of daily living (BADL),[17],[18] and NIH stroke scale (NIHSS).[19],[20] The outcome was dichotomized on the basis of mRS score into poor (>3) and good (MRS 0–2) outcome.[21] In BADL, the total possible scores range from 0 to 20, with lower scores indicating increased disability.[17]
Statistical analysis
The baseline characters were expressed as percentages or mean and standard deviation depending on the type of variable (categorical or continuous). Independent samples t-test was used to compare means of continuous variables and Chi-square test for categorical variables. The P value < 0.05 was considered significant.
ResultsDemographic and clinical profile
During the study period 100 consecutive patients of NS-LST were seen. The flow of the patients and sinus involvement pattern is shown in [Figure 1]. Females (n = 56 (56%), puerperiumn = 22 (39.28%)) were commonly affected than males (n = 44 (44%)). The mean age at the onset was 31.45 ± 11.13 years. It was lower in females (29.6 ± 11.35 years) compared with males (33.7 ± 10.55 years, P value 0.07). The majority of patients were lower socioeconomic class (n = 76 (76%)) and from the rural background (n = 63 (63%)). The demographic profile was similar in patients with isolated (n = 27) and combined LST (n = 73) groups [Table 1]. The common presenting symptoms were headache (97%), nausea and vomiting (67%), seizures (46%), weakness (35%), and language disturbances (26%) [Table 1].
Figure 1: Flow of patients with non-septic lateral sinus thrombosis, pattern of sinus involvement and outcome
Table 1: Clinical symptoms of patients with Lateral Sinus thrombosis at presentation (n=100)The clinical profile of the patients is summarized in [Table 1] and [Supplementary Table 1] and [Supplementary Table 2]. Briefly, sub-acute onset (n = 74) was common in both groups (isolated LST n = 19, combined LST n = 55). The left LST involvement was commonly associated with isolated LST (in 50%) and right and bilateral LST was associated with combined LST. The mode of presentation was different between the two groups with IIH being common and encephalopathy less frequent in isolated LST patients [Table 1]. It was interesting to note that there was difference in mode of presentation with side of lateral sinus involved [Supplementary Table 2]. Isolated IIH like presentation was common with right and bilateral LST and focal deficits with left LST. Bilateral LST was seen in 13 patients.
Risk factors
Hyperhomocysteinemia (61%), anemia (57%), puerperium (39.28%), oral contraceptive pill (OCP) intake (35.29%, n = 12), low serum B12 (32%), and polycythemia (15%) were the common risk factors observed. Multiple risk factors were noted in 76% of the patients [Table 2] and [Supplementary Table 3]. Significant gender differences were noted [Supplementary Table 3].Anemia was more common in females (82.1%, n = 46) and highly prevalent in puerperal (90.9%, n = 20) patients. The other risk factors noted in puerperium were dehydration due to fluid restriction (40.9%, n = 9) and excessive bleeding (22.7%, n = 5) during delivery. Anemic females also had other risk factors such as oral contraceptive intake (23.9%, n = 11) and low vitamin B12 (32.6%, n = 15). In males, polycythemia (31.8%, n = 14) and hyperhomocysteinemia (70.5%, n = 35) were common. All males with polycythemia were active smokers and majority consumed alcohol. Anemia was noted in 25% (n = 11) males.
Table 2: Risk factor profile of patients with Lateral sinus thrombosis during admission (n=100)Imaging profile
Computerized tomography had an overall sensitivity of 67% (57.6%, n = 15 in isolated and 70.4%, n = 50 of combined LST patients). Magnetic resonance imaging (MRI) brain had an advantage of defining the stage of thrombosis, detecting subtle parenchymal abnormalities, microhemorrhages, and additional sinus involvement compared with CT brain [Table 3] and [Table 4]. It was also more sensitive in the diagnosis of cortical vein thrombosis compared with CT brain (31% vs. 15.46%; P value 0.01). In combined LST, superior sagittal sinus was most frequently involved (89%, n = 65) followed by cortical veins (42%, n = 31) and deep venous system (23%, n = 17). The combination of lateral sinus, superior sagittal sinus, and cortical vein thrombosis (34.24%, n = 25) was frequently observed. Right lateral sinus (55.5%, n = 15) was commonly associated with Superior sagittal sinus thrombosis compared with left lateral sinus (19.23%, n = 5). Follow-up imaging was available in 39.5% (n = 38) patients. The mean duration between two MRI images was 5.42 ± 3.09 months. The sinus recanalization was present in 39.5% (n = 15), absent in 55.3% (n = 21), and partial in 5.2% (n = 2).
Table 3: Magnetic resonance imaging (MRI) findings in patients with lateral sinus thrombosis during at presentation (n=100)
Table 4: Comparison of CT and MRI of Brain imaging studies in patients with lateral sinus thrombosis at presentation (n=100)Management
Mean duration of hospitalization was 15.14 ± 6.85 days. All patients were treated with initial heparin followed by oral vitamin K antagonists. Risk factors were treated (anemia, polycythemia, Vit B12 deficiency) according to standard practices. Decompressive craniectomy was done in 11 patients during the acute phase (n = 2, isolated LST; n = 9, combined LST) for raised intracranial pressure and brainstem compression due to mass effect. Four patients (oneisolated andthree combined LST) died during hospitalization. The isolated LST patient had cerebellar bleed with brainstem compression which progressed despite suboccipital decompressive craniectomy. In patients with combined LST, one patient had meningitis postdecompressive craniectomy; one had pneumonia and one probable pulmonary embolism secondary to axillary and brachiocephalic vein thrombosis. All patients died during the acute phase and no mortality was noted during follow-up.
Prognosis
In this study, the mortality was 4% and at 3 months the overall outcome was good in 81% (n = 81) and poor in 19% (n = 19) on the basis of modified Rankin score (mRS 0–2 vs. 3–6). Patients with combined LST had more severe disease at admission compared with isolated LST group as reflected modified Rankin score (2.84 vs. 2.25; P value = 0.05) and NIHSS (6 vs 2.96; P value = 0.04), BADL (12.83 vs. 17.55; P value = 0.06) in these patients. The overall functional outcome was favorable and similar in both the groups during follow-up [Table 5]. However, greater number of isolated LST patients (88.8%, n = 24) were functionally independent (mRS <2) compared with the combined LST (78%, n = 57) group [Supplementary Table 4].Three-fourth of overall study group was able to resume their employment during the follow-up period. We compared the baseline demographic, clinical, and imaging profile between good and poor outcome (mRS 0-2 vs >3) groups to determine the prognostic factors (data not shown). In univariate analysis, low GCS (<8 on Glasgow coma scale) at presentation, the presence of hemiparesis, combined LST, and cerebellar involvement on imaging and decompressive craniectomy were statistically significant factors at baseline that predicted the poor outcome. In this study, all the 96 patients came for follow-up for a mean duration of 6.5 ± 4.05 months. Headache (n = 29), residual hemiparesis (n = 13), seizures (n = 7), and visual impairment (n = 6) were the symptoms noted at the follow-up.
Table 5: Summary of Functional outcome of patients with Lateral sinus thrombosis at 3 months (n=100) Discussion The present prospective, single center, large cohort study of patients with NS-LST shows that it predominantly affects young males and females in their productive years, isolated LST being less common. These patients present sub acutely with headache, seizures, focal deficits, and features of raised intracranial pressure. Risk factors are seen in majority and are physiological states, nutritional deficiencies, and habits, which can be easily corrected or treated. Imaging with MRI offers distinct advantages over CT scan. Majority of patients improve with anticoagulation and supportive treatment and 11%may require surgery. Mortality is low and predominantly during acute phase.
The demographic profile of our patients showed female predominance and patients mainly from rural and lower socioeconomic background. The female preponderance is due to gender-specific risk factors such as oral contraceptive use, pregnancy, and puerperium.[22] Certain risk factors such as nutritional anemia and cultural practices like withholding fluid intake in immediate postpartum state are common in rural people with the low socioeconomic state.[3] This demographic profile is changing with two recent CVT studies from urban India showing a male predominance.[23],[24]
The clinical presentation is similar to CVT in general with a headache, vomiting, seizures, and weakness as presenting symptoms. Seizures and weakness were more frequent in the combined LST group probably reflecting the involvement of other areas of brain apart from temporal lobes. Aphasia was more common in isolated group and it was Wernicke's type, related to the temporal lobe involvement. The mode of presentation is determined by the extent of thrombosis, presence of parenchymal lesions, and presence of adequate collateral circulation. A presentation such as IIH Idiopathic intracranial Hypertension (IIH) like presentation results from impaired CSF absorption due to dural sinus thrombosis. The extension of dural sinus thrombus to adjacent cerebral veins in absence of adequate collaterals leads to a focal increase in pressure producing venous infarction and focal deficits.[1],[2] Patients often have more than one clinical feature at presentation or during the course of illness as seen in our present cohort reflecting the dynamic nature of disease process.[25]
The prevalence of IIH like presentation in isolated LST group (44%) is higher in this study compared with 10%–24% in other series.[4],[26] Right (41%) and bilateral (54%) LST were common compared with left LST (15%). The right lateral sinus is usually the dominant sinus and receives a large drainage from the superior sagittal sinus; while left transverse sinus is smaller and drains the straight sinus.[27] Similar right-sided commonality in IIH was noted in a previous study.[4]
Headache as the sole manifestation of CVT was rare in our study 2 (2%). This is in contrast to a higher prevalence (45% isolated, 9% combined LST) noticed in another study.[4] The characteristics of a headache were also not localizing in contrast to another study which found occipital and neck pain to be more common in LST patients.[28] The possible mechanisms for a headache in CVT include raised intracranial pressure, venous congestion/cortical vein thrombosis, stretching of nerve fibers in thrombosed sinus, and local inflammation.[10],[29] Papilledema was a frequent finding on examination seen in more than half of our subjects. It was less common in isolated LST similar to an earlier study.[4] Interestingly, all patients with isolated LST and papilledema had IIH as the mode of presentation.
Hyperhomocysteinemia is a well-recognized although the less frequent cause of CVT (4.5%) in western studies.[27] The causes include nutritional factors such as cobalamine, pyridoxine, and folic acid deficiency and genetic factors such as methylene tetrahydrofolatereductase (MTHFR) enzyme deficiency.[30] Smoking also increases serum homocysteine level.[31] The incidence in our study (61%) is higher than 18% noted in a large CVT study from southern India.[23] It is probably due to nutritional factors as the prevalence of poverty and other nutritional risk factors like low vitamin B12 were high in our patients. Many of these patients were also active smokers. Low vitamin B12 was another risk factor prevalent our study. It was both due to nutritional deficiency and dietary habits such as strict vegetarian state. None of these patients had pernicious anemia. Significant gender differences were observed in the risk factors. Anemia was common in females and was highly prevalent in puerperal women.
The risk factors in our study are in concordance with other CVT studies in developing countries with the predominance of anemia and postpartum state.[32],[33] This is in contrast to western studies where genetic causes of prothrombotic state, such asAntithrombin III, Protein C, S deficiency, Prothrombin G20210A, factor V Leiden gene mutation, and resistance to activated protein C, contributes to around 34% of patients.[25] These differences might also reflect a reporting bias as prothrombotic factors are not actively investigated among CVT patients in developing countries.[34] In the recent CVT studies from India, genetic prothrombotic conditions accounted for 12%–18% of all CVT patients.[23],[24]
The sensitivity of CT brain in our study (67%) was similar to 60%–70%noted in other studies.[4],[21],[35] CT brain has the advantage of round theclock availability and shorter scanning time,th at helps to easilyperform it in acute settings.[25] The disadvantages include lesser sensitivity to detect hyperdense sinus due to the adjacent skull, difficulty in differentiating thrombosis from arachnoid granulation, and sinus hypoplasia. Hyperdense sinus can also be seen in other conditions such as dehydration and polycythemia.[36] The other drawbacks include ionizing radiation, contrast nephropathy, and allergy. MRI brain has an advantage of direct thrombus visualization, delineating the stage of thrombus and also ruling out CVT mimics such as hypoplasia and arachnoid granulations which are frequent in the lateral sinus.[25] It is also more sensitive than CT in the diagnosis of cortical vein thrombosis. In patients with combined LST, superior sagittal sinus and cortical vein were frequently involved. The combination of right LST with superior sagittal sinus thrombosis (55.5%) was more frequent than with left LST (19.2%); which can be explained by the anatomical factors.[27] The incidence of cortical vein thrombosis (31%) was significantly >17% described in CVT studies. This might have contributed to the higher frequency of hemorrhagic infarcts (79%) noted in our study. The deep venous sinus system was also more frequently affected (17%) compared with 11% noted in the CVT studies.[25]
In this study, four patients (one isolated LST, threecombined LST) died during the acute phase and no deaths were recorded during follow-up. The low mortality in isolated LST is similar to other studies. In a study of 62 isolated LST patients, one patient died during the acute phase and one during 1-year follow-up.The predictors of early mortality like low GCS at admission and posterior fossa involvement as found inother CVT studies were also noted in our present cohort; whereas no mortality was seen in patients with deep venous sinus thrombosis.[25]
The limitations of our study are genetic tests for prothrombotic states such as protein C, S, and antithrombin level were not done due to cost concerns. The diagnosis of IIH was based on clinical examination, and CSF pressure analysis measurement was not done. Only half of the studied population patients under went repeat imaging; hence, the correlation of symptoms on follow-up with recanalization could not be definitively established.
ConclusionsOur group of patients with NS-LST had a distinctive demographic profile and associated risk factors. The clinical features depend on the side of sinus involvement, presence of another sinus, and/orcorticalvein involvement. Imaging with MRI has many advantages over CT. Anticoagulation and supportive treatment is associated with good out come in majority.
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.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Supplementary
References
留言 (0)