Cerebralvenous sinus thrombosis (CVST) is a rare cause of pediatric stroke with a reported incidence of 0.67 cases per 100,000 children per year, although there is widespread acknowledgment that the diagnosis is likely underrecognized.1–3在新生儿期之外,头部和颈部发生ctions are frequently associated with pediatric CVST, accounting for up to 65% of cases in some series.1,3–6Septic thrombosis of the cerebral venous sinuses results from bacterial spread via emissary veins or via direct extension from adjacent infections, which produces thrombophlebitis.7Several patterns of septic CVST have been described, including cavernous sinus thrombosis, otogenic lateral sinus (transverse and/or sigmoid sinus) thrombosis, and sinogenic superior sagittal sinus thrombosis.8
Septic CVST has the potential to result in significant neurological morbidity and mortality, although outcomes have improved in the antibiotic era.3,9,10Treatment typically includes hydration, surgical management of the infection, and administration of parenteral antibiotics, but the use of anticoagulation remains controversial. Proponents of anticoagulation highlight its role in preventing thrombus propagation and promoting recanalization.11,12Those who recommend against the routine use of anticoagulation for pediatric septic CVST cite the risk of hemorrhagic complications and reports of good clinical outcomes without anticoagulation.9,13,14As a result, pediatric guidelines vary. The American Society of Hematology recommended anticoagulation for all pediatric patients with CVST without hemorrhage,15while the American Heart Association and American Stroke Association recommended a multidisciplinary, patient-specific approach for pediatric patients with septic CVST, suggesting that recanalization rates are high after surgery and antibiotic therapy, but that anticoagulation should be considered for patients with evidence of thrombus propagation.15
Therapeutic anticoagulation is even more controversial in the acute postoperative period after an intracranial procedure, such as a craniotomy for an epidural abscess or subdural empyema (Fig. 1）.This issue has become particularly relevant recently, as we identified a threefold increase in the frequency of pediatric sinogenic and otogenic intracranial infections at Connecticut Children’s during the COVID-19 pandemic.16All patients underwent emergency neurosurgical treatment of the infection, but a subset of these patients was also found to have a septic CVST. Here, our objective was to study the diagnosis, management, and outcomes of septic CVST within this patient population across 3 centers and to explore the safety and efficacy of therapeutic anticoagulation following neurosurgical intervention for sinogenic or otogenic intracranial infections.
Schematic overview of the relationship between sinusitis, otitis media and/or mastoiditis, intracranial infection, and septic CVST. Management strategies include surgical washout of the infection, parenteral antibiotics, and hydration, although the role of anticoagulation remains controversial. © David Hersh, published with permission.
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Patient Cohort
This study included patients from Connecticut Children’s, Rady Children’s Hospital–San Diego, and Ann and Robert H. Lurie Children’s Hospital of Chicago. The study was approved by the local IRBs at each institution. All pediatric patients (≤ 21 years of age) who presented with an intracranial infection in the setting of acute or chronic otitis media and/or sinusitis and underwent a neurosurgical procedure for treatment of the infection between March 2015 and March 2023 were included. Exclusion criteria included surgical site or postoperative infections, CSF shunt-related intracranial infections, and a remote history of sinusitis or otitis media that was not related to the current intracranial infection. Some features of the Connecticut Children’s cohort were previously reported in an epidemiological study.16
Data Collection
医疗侦察rds were retrospectively reviewed. Data were collected regarding the demographics and clinical presentation of all patients. For patients with a CVST, data were also collected regarding the radiological features of the thrombosis, management, complications, and outcomes.
Statistical Analysis
Descriptive statistics were performed using median and IQR for continuous variables and frequency and percentage for categorical variables. Fisher’s exact test was used to compare categorical variables between the CVST and non-CVST cohorts. Independent-sample t-tests and Mann-Whitney U-tests were used to compare the distributions of normally or nonnormally distributed continuous variables, respectively; two-tailed p < 0.05 was considered significant.
Results
Patient Characteristics
During the study period, 96 patients were diagnosed with sinogenic or otogenic intracranial infections requiring neurosurgical intervention. Sixteen (16.7%) patients were treated at Connecticut Children’s, 42 (43.8%) at Rady Children’s Hospital–San Diego, and 38 (39.5%) at Ann and Robert H. Lurie Children’s Hospital of Chicago (Fig. 2）.Overall, 86 (89.6%) patients were diagnosed with sinogenic infections, while 11 (11.5%) had otogenic infections, including 1 patient who had both sinogenic and otogenic infections. Fifteen (15.6%) patients were diagnosed with a septic CVST, including 12 (14.0%) of the patients with sinogenic infections and 3 (27.3%) of the patients with otogenic infections.
Summary of patients with sinogenic or otogenic intracranial infection and septic CVST.
Patient characteristics are summarized inTable 1。总的来说,没有明显差异etween patients with a CVST and those without a CVST. The median age at the time of the first neurosurgical procedure was 11.4 (IQR 7–14) years in the CVST cohort and 11.0 (IQR 8.6–14.0) years in the non-CVST cohort (p = 0.649). Among patients with a CVST, none had a documented personal or family history of thrombosis. Furthermore, none of the patients had a documented history of smoking, exposure to secondhand smoke, or use of oral contraceptives. Two (2.1%) patients had documented obesity (BMI > 30), one in the CVST cohort and one in the non-CVST cohort, although these data were not consistently recorded.
Patient characteristics
| Characteristic | 所有分(n = 96) | CVST (n = 15) | No CVST (n = 81) | p Value |
|---|---|---|---|---|
| 男性sex, n (%) | 63 (65.6) | 9 (60.0) | 54 (66.7) | 0.618 |
| Race, n (%)* | 0.281 | |||
| White or Caucasian | 44 (45.8) | 5 (33.3) | 39 (48.1) | |
| Black or African American | 21 (21.9) | 6 (40.0) | 15 (18.5) | |
| Other | 27 (28.1) | 3 (20.0) | 24 (29.6) | |
| Not specified | 4 (4.2) | 1 (6.7) | 3 (3.7) | |
| Ethnicity, n (%) | 0.372 | |||
| Not Hispanic or Latino | 65(67.7) | 12 (80.0) | 53 (65.4) | |
| Hispanic or Latino | 31 (32.3) | 3 (20) | 28 (34.6) | |
| English as preferred language, n (%) | 86 (89.6) | 13 (86.7) | 73 (90.1) | 0.687 |
| Insurance type, n (%) | 0.916 | |||
| Public | 46 (47.9) | 7 (46.7) | 39 (48.1) | |
| Private | 50 (52.1) | 8 (53.3) | 42 (51.9) | |
| Median age at op (IQR), yrs | 11.0 (8.1–14.0) | 11.4 (7.0–14.0) | 11.0 (8.6–14.0) | 0.649 |
| Otolaryngological association, n (%) | 0.318 | |||
| Sinusitis | 85 (88.5) | 12 (80.0) | 73 (90.1) | |
| Otitis media | 10 (10.4) | 3 (20.0) | 7 (8.6) | |
| Both | 1 (1.04) | 0 (0) | 1 (1.2) | |
| Presented during COVID-19, n (%) | 36 (37.5) | 9 (60.0) | 27 (33.3) | 0.050 |
Thirty-six (37.5%) patients with an intracranial infection presented during the 3 years of the COVID-19 pandemic, compared with 60 (62.5%) patients who presented during the 5 years prior to the COVID-19 pandemic (p = 0.07). Of the 60 patients who presented with a sinogenic or otogenic intracranial infection prior to the COVID-19 pandemic, 6 (10.0%) were diagnosed with a septic CVST, whereas of the 36 patients who presented during the COVID-19 pandemic, 9 (25.0%) had a septic CVST (p = 0.050). Of the patients with a CVST who presented during the COVID-19 pandemic, none had a documented SARS-CoV-2 infection when they presented. A history of previous SARS-CoV-2 infection(s) and the patients’ vaccination status were not consistently recorded.
Clinical Presentation and Neurosurgical Intervention
The presenting features, anatomical distribution of the infection, and neurosurgical interventions are summarized inTable 2。Common presenting signs and symptoms included headache (73.3% in the CVST cohort vs 64.2% in the non-CVST cohort, p = 0.494), fever (60.0% vs 54.3%, p = 0.685), and facial swelling (33.3% vs 23.5%, p = 0.417). Among patients with a CVST, symptoms were present for less than 1 week in 8 (53.3%) patients, 1–4 weeks in 7 (46.7%) patients, and more than 4 weeks in none of the patients. In contrast, among patients without a CVST, symptoms were present for less than 1 week in 28 (34.6%) patients, 1–4 weeks in 46 (56.8%) patients, and more than 4 weeks in 4 (5.0%) patients (p = 0.618). The duration of symptoms was not documented for 2 (2.5%) patients.
Clinical presentation and neurosurgical intervention
| Variable | 所有分(n = 96) | CVST (n = 15) | No CVST (n = 81) | p Value |
|---|---|---|---|---|
| Presentation, n (%)* | ||||
| Headache | 63 (65.6) | 11 (73.3) | 52 (64.2) | 0.494 |
| Fever | 53 (55.2) | 9 (60.0) | 44 (54.3) | 0.685 |
| Facial swelling | 24 (25.0) | 5 (33.3) | 19 (23.5) | 0.417 |
| Neck stiffness | 3 (3.1) | 1 (6.7) | 2 (2.5) | 0.403 |
| Other | 75 (78.1) | 10 (66.7) | 65 (80.2) | 0.243 |
| Symptom onset, n (%) | 0.618 | |||
| >4 wks prior | 4 (4.2) | 0 (0) | 4 (5.0) | |
| 1–4 wks prior | 53 (55.2) | 7 (46.7) | 46 (56.8) | |
| <1 wk prior | 36 (37.9) | 8 (53.3) | 28 (34.6) | |
| Not documented | 2 (2.1) | 0 (0) | 2 (2.5) | |
| Sinus involvement, n (%) | ||||
| Frontal sinus | 76 (79.2) | 11 (73.3) | 65 (80.2) | 0.545 |
| Ethmoid sinus | 55 (57.3) | 6 (40.0) | 49 (60.5) | 0.141 |
| Intracranial infection, n (%)* | ||||
| Epidural abscess | 52 (54.2) | 11 (73.3) | 41 (50.6) | 0.158 |
| Subdural empyema | 50 (52.6) | 8 (53.3) | 42 (52.5) | 0.953 |
| Cerebral abscess | 9 (9.4) | 1 (6.7) | 8 (9.9) | >0.99 |
| Pott’s puffy tumor, n (%) | 23 (24.0) | 5 (33.3) | 18 (22.2) | 0.354 |
| Total neurosurgical procedures | 123 | 20 | 103 | |
| Median neurosurgical procedures/pt (IQR) | 1 (1–1) | 1 (1–2) | 1 (1–1) | 0.629 |
| Type of neurosurgical procedure, n (%)† | ||||
| Burr hole | 17 (13.8) | 2 (10) | 15 (14.6) | 0.754 |
| Craniotomy | 86 (69.9) | 14 (70) | 72 (69.9) | 0.830 |
| Craniectomy | 19 (15.4) | 4 (20) | 15 (14.6) | 0.471 |
| Other | 1 (0.8) | 0 (0) | 1 (0.97) |
More than one option was possible.
Calculated as a percentage of the total craniotomies and craniectomies.
Infections involved the frontal sinuses (73.3% in the CVST cohort vs 80.2% in the non-CVST cohort, p = 0.545), ethmoid sinuses (40.0% in the CVST cohort vs 60.5% in the non-CVST cohort, p = 0.141), and middle ear and/or mastoid (20.0% in the CVST cohort vs 9.9% in the non-CVST cohort, p = 0.370). Intracranially, epidural abscesses were identified most frequently (73.3% in the CVST cohort vs 50.6% in the non-CVST cohort, p = 0.158), followed by subdural empyemas (53.3% in the CVST cohort vs 52.5% in the non-CVST cohort, p = 0.953) and intraparenchymal abscesses (6.7% in the CVST cohort vs 9.9% in the non-CVST cohort, p > 0.99). Five (33.3%) patients were diagnosed with a Pott’s puffy tumor in the CVST cohort compared with 18 (22.2%) patients in the non-CVST cohort (p = 0.354).
The 15 patients in the CVST cohort underwent a total of 20 neurosurgical procedures to wash out the intracranial infection (median 1 procedure per patient, IQR 1–2 procedures), of which 70.0% were craniotomies, 20.0% were craniectomies, and 10.0% were burr holes. The 81 patients in the non-CVST cohort underwent a total of 103 neurosurgical procedures (median 1 procedure per patient, IQR 1–1 procedure), of which 69.9% were craniotomies (p = 0.830), 14.6% were craniectomies (p = 0.471), and 14.6% were burr holes (p = 0.754).
Imaging Studies
Radiological features are summarized inTable 3。Of the 15 patients diagnosed with a septic CVST, 13 (86.7%) were diagnosed via MRI, 1 (6.7%) via CT, and 1 (6.7%) via both MR and CT. Eleven (73.3%) patients were diagnosed prior to the first neurosurgical procedure, while 4 (26.7%) patients were diagnosed postoperatively.
Radiological features of patients with a septic CVST (n = 15)
| Variable | No. of Pts (%) |
|---|---|
| Imaging modality | |
| MRI | 13 (86.7) |
| CT | 1 (6.7) |
| MRI & CT | 1 (6.7) |
| Timing of diagnosis | |
| Preop | 11 (73.3) |
| Postop | 4 (26.7) |
| Venous involvement* | |
| Superior sagittal sinus | 12 (80.0) |
| Anterior 1/3 | 8 (53.3) |
| Middle 1/3 | 7 (46.7) |
| Posterior 1/3 | 2 (13.3) |
| 横向和/或乙状窦 | 4 (26.7) |
| Cortical vein thrombosis | 2 (13.3) |
| Internal jugular involvement | 2 (13.3) |
| Fully occlusive thrombosis | 1 (6.7) |
| Intracerebral hemorrhage at time of diagnosis | 0 (0) |
More than one option was possible.
Twelve (80.0%) patients had involvement of the superior sagittal sinus. Of these, the anterior third of the superior sagittal sinus was involved in 8 (66.7%) patients, the middle third in 7 (58.3%) patients, and the posterior third in 2 (16.7%) patients. The transverse and/or sigmoid sinuses were involved in 4 (26.7%) patients. Two (13.3%) patients had involvement of the internal jugular vein, and 2 (13.3%) also experienced a cortical vein thrombosis. Only 1 (6.7%) patient had a fully occlusive thrombus. None of the patients had an intracerebral hemorrhage at the time of the CVST diagnosis.
Anticoagulation
All patients underwent a neurosurgical procedure to wash out the intracranial infection and were initiated on parenteral antibiotics. Of the 15 patients with a septic CVST, 11 (73.3%) were initiated on anticoagulation (Fig. 3）.从最近的某些区间中值urgical procedure to the initiation of anticoagulation was 4 (IQR 3–5) days. Treatment paradigms varied and were determined on a case-by-case basis. Four patients were initially placed on an intravenous heparin drip; 3 were subsequently transitioned to subcutaneous enoxaparin, and 1 was transitioned to oral rivaroxaban for the duration of their treatment. Three patients were treated with subcutaneous enoxaparin and were subsequently transitioned to oral rivaroxaban prior to discharge. Four were treated with subcutaneous enoxaparin for the duration of their treatment.
Individual patient responses to septic CVST treatment. Length of hospitalization, neurosurgical interventions, type of anticoagulation, and recanalization status on follow-up imaging are represented.
Patients with a septic CVST had a median length of stay of 16 (IQR 9–20) days, whereas patients without a CVST had a median length of stay of 11 (IQR 8–18.75) days (p = 0.281). Of the 11 patients treated with anticoagulation, 7 (63.6%) patients were discharged with subcutaneous enoxaparin and 4 (36.4%) were discharged with oral rivaroxaban. The median duration of anticoagulation was 3 (IQR 2.7–3.0) months, with the longest duration of anticoagulation being 5.03 months.
Outcomes
The median follow-up duration was 5.0 (IQR 2.0–12.0) months. Of the 11 patients with a CVST who were treated with anticoagulation, 10 (90.9%) returned to their neurological baseline, and 1 (9.1%) reported persistent headaches and nighttime awakening. All 4 of the patients with a CVST who did not undergo anticoagulation returned to their neurological baseline. Of the remaining 81 patients without a CVST, 1 patient died, 1 patient developed a seizure disorder, and 2 had a persistent hemiparesis; the remaining patients returned to their neurological baseline. Complications were uncommon. None of the patients treated with anticoagulation exhibited intracranial or extracranial hemorrhagic complications. One patient required a neurosurgical procedure after a heparin drip had been initiated; anticoagulation was held for the procedure and was restarted 2 days later.
Of the 15 patients with a septic CVST, 13 (86.7%) underwent follow-up venous imaging. Five (45.5%) patients who underwent anticoagulation demonstrated complete recanalization on their latest scan, and 4 (36.4%) had partial recanalization (Fig. 4A）.Three (75.0%) patients who did not undergo anticoagulation demonstrated complete recanalization, and 1 (25.0%) had partial recanalization (Fig. 4B）.Overall, the median interval to complete recanalization was 2 (IQR 1–2.75) months. None of the patients in this series developed clinical signs of intracranial hypertension or underwent CSF diversion.
Illustrative cases depicting the management of CVST in patients with sinogenic and/or otogenic intracranial infections.A:An 11-year-old boy presented with worsening fevers and headaches. A head CT scan and subsequent MR image/MR venogram demonstrated frontal, ethmoidal, and left maxillary sinusitis with a secondary epidural abscess (arrowsinleftimages) along the midline anterior frontal convexity and extrinsic compression of the anterior portion of the superior sagittal sinus. An endoscopic maxillary antrostomy and ethmoidectomy was performed concurrently with a bifrontal craniotomy for evacuation of the epidural abscess. Postoperative imaging continued to demonstrate a filling defect (arrowincenterimage) within the midportion of the superior sagittal sinus. Enoxaparin was initiated on postoperative day 3 and was continued for 3 months, at which point a repeat MR venogram demonstrated patent venous sinuses (arrowinrightimage). There were no hemorrhagic complications.B:A 14-year-old girl presented with fevers, scalp swelling, and headaches. MR images revealed intracranial extra-axial abscesses adjacent to the right mastoid, extracranial abscesses involving the right parieto-occipital scalp, and intracranial abscesses in the right parietal and occipital lobes (arrowsinleftimages). A nonocclusive thrombus was noted in the right transverse sinus, as well as within the right internal jugular vein (arrowincenterimage). The patient was taken to the operating room for right parietal and posterior fossa craniotomies for abscess drainage, in addition to a mastoidectomy. Postoperative imaging demonstrated unchanged thromboses. The patient was not treated with anticoagulation, and the thromboses completely resolved on follow-up imaging 1 month later (arrowinrightimage). ED = emergency department.
Discussion
Pediatric CVST is rare but has the potential to lead to significant neurological morbidity and mortality. Septic CVST, in particular, is frequently associated with sinogenic and otogenic intracranial infections, which have become more prevalent during the COVID-19 pandemic.16Treatment includes hydration, surgical (otolaryngological and neurosurgical) intervention for the infection, and parenteral antibiotics, but the role of anticoagulation is controversial, especially in the context of a recent neurosurgical procedure for an epidural abscess or subdural empyema. Therefore, we investigated the diagnosis, management, and outcomes of pediatric patients at 3 referral centers across the United States with sinogenic or otogenic intracranial infections and a septic CVST. We found that approximately 15% of patients undergoing neurosurgical intervention for a sinogenic or otogenic intracranial infection were diagnosed with a septic CVST, 73% of whom were treated with anticoagulation. Although there were no significant hemorrhagic complications, the patients who did not undergo anticoagulation also demonstrated good radiological and clinical outcomes over a similar time frame.
Efficacy of Anticoagulation
Treatment recommendations for pediatric CVST were initially extrapolated from randomized clinical trials involving adults,17–19但儿科病例分析和观察性研究s have demonstrated the efficacy of anticoagulation among pediatric patients as well. In a prospective cohort study, deVeber et al. found that 3 of 8 untreated pediatric patients with CVST died, compared with 0 of 22 patients treated with anticoagulation.20Subsequently, Sébire et al. studied 42 children with CSVT from 5 European pediatric neurology stroke registries.3Eighteen (43%) were treated with anticoagulation, which was found to be an independent predictor of good cognitive outcome.3There is also evidence that anticoagulation affects recanalization rates; in a pooled European collaborative study involving 396 patients with CVST, 250 (63%) underwent anticoagulation, which reduced the risk of a recurrent thrombosis.21Similarly, Moharir et al. reported that among 162 pediatric patients with CVST, 85 (52%) were treated with anticoagulation, which was associated with a lower risk of thrombus propagation.22As a result, the American Society of Hematology 2018 Guidelines recommended anticoagulation for pediatric patients (beyond the newborn period) diagnosed with CVST.15
Some have proposed that a subset of patients might achieve recanalization without anticoagulation, thereby reducing the medication-related costs, the frequency of follow-up visits, the number of follow-up imaging studies, and the hemorrhagic risks associated with anticoagulation. Indeed, in the current series, 4 patients were not treated with anticoagulation, 3 of whom demonstrated full sinus recanalization and 1 of whom demonstrated partial recanalization on follow-up imaging. Others have even questioned the clinical significance of sinus recanalization, pointing out examples of good clinical outcomes even in the absence of recanalization.9,13,23,24As a result, the American Heart Association and American Stroke Association recommended a multidisciplinary, patient-specific approach for patients with septic CVST, acknowledging that the role of anticoagulation remains controversial and suggesting that surgical intervention and broad-spectrum antibiotics are the mainstays of treatment.25In cases without an abscess or empyema, a lumbar puncture may also be considered to confirm the presence of meningitis, which can impact the decision to incorporate antibiotics that penetrate the blood-brain barrier.
In a meta-analysis of cases of pediatric CVST following acute mastoiditis, anticoagulation was administered in 86% of studies for a median duration of 3 months, while otological surgery was performed in 91% and broad-spectrum antibiotics were administered in 100%.26Anticoagulation regimens may include parenteral unfractionated heparin, subcutaneous low-molecular-weight heparin (e.g., enoxaparin), oral warfarin, or newer direct oral anticoagulant agents.6Parenteral unfractionated heparin has the advantage of a short half-life; the medication can be discontinued if another procedure is required or if a hemorrhagic complication is encountered. Conversely, low-molecular-weight heparin has demonstrated superior safety and efficacy in studies involving patients with CVST.27,28Low-molecular-weight heparin typically has a predictable effect, can be provided in fixed weight-adjusted doses, and is often preferred as the initial treatment agent.9,22Beyond the acute phase of therapy, there are now additional treatment options such as rivaroxaban and dabigatran, which have more recently been approved for use in pediatric patients. A subgroup analysis of the EINSTEIN-Jr trial (Oral Rivaroxaban in Children With Venous Thrombosis) involving rivaroxaban demonstrated that patients with CVST had a low risk of recurrent thrombosis or clinically significant bleeding compared with patients treated with standard anticoagulation.29In our own series, a variety of treatment paradigms were used and varied by institution. Some patients were placed on an intravenous unfractionated heparin infusion during the immediate postoperative period and were later transitioned to subcutaneous enoxaparin. Others were initiated on subcutaneous enoxaparin, with some later transitioned to oral rivaroxaban. Although 3 months of anticoagulation are often recommended, the median interval to recanalization was only 2 months in the current study. Recent studies have suggested that shorter durations of anticoagulation may be sufficient.30However, long-term follow-up is needed to determine the rates of CVST recurrence or propagation after anticoagulation is discontinued.
Safety of Anticoagulation
Despite evidence supporting the efficacy of anticoagulation, hemorrhagic complications remain a concern. Among patients with otogenic lateral sinus thromboses treated with enoxaparin, Shah et al. identified 2 cases of postoperative hemorrhage and Funamura et al. reported 1 intracranial hemorrhage that resulted in early discontinuation of anticoagulation.9,31Conversely, Ropposch et al. presented 6 patients treated with unfractionated heparin for 3 days followed by enoxaparin for 3 months, none of whom experienced hemorrhagic complications.11在一个大型前瞻性研究涉及儿科patients with a CVST of any etiology, Moharir et al. found that 6% of patients treated with anticoagulation had a major hemorrhagic event (classified as a hemoglobin drop of > 2 g/dL or the need for a blood transfusion), although none were fatal and the patients had similar clinical outcomes relative to those without a hemorrhage.22Similarly, in the Canadian Pediatric Ischemic Stroke Registry, there were no fatal or severe complications among the 85 pediatric patients with CVST treated with anticoagulation.2Ultimately, a Cochrane review concluded that anticoagulation is safe for the treatment of pediatric CVST and may reduce mortality.32
Initiating anticoagulation following a neurosurgical procedure, however, is a unique situation that is not specifically addressed by CVST treatment guidelines, given the putatively higher risk of intracranial hemorrhage in this context. Much of the prior literature has focused on adults. A systematic review of 243 adult patients with CVST who underwent anticoagulation following a decompressive craniectomy concluded that anticoagulation could be safely initiated or resumed 24–48 hours postoperatively.33Most recently, the EINSTEIN-Jr CVT investigators performed a subgroup analysis of pediatric patients with CVST and an associated head or neck infection who received therapeutic anticoagulation.34Of the 34 patients who were diagnosed with CVST prior to surgical intervention, anticoagulation was restarted at a median of 1 day postoperatively, with no episodes of major bleeding associated with surgery. The authors concluded that there was a low risk of bleeding associated with anticoagulation in this patient population.
Impact of COVID-19
In this study, we identified a higher rate of septic CVST during the COVID-19 pandemic compared with the 5-year period preceding the pandemic (25% vs 10% of patients, p = 0.05). CVST has previously been reported following vector-based COVID-19 vaccination in adults, particularly in the setting of thrombosis-thrombocytopenia syndrome.35,36Others have also documented an association between SARS-CoV-2 infection and venous thromboembolic complications, including CVST.37–41SARS-CoV-2 infection may induce a hypercoagulable and hyperinflammatory state through several mechanisms, including depletion of angiotensin-converting enzyme 2 receptors, antiphospholipid antibody production, and activation of the coagulation pathway by viral particles and damage-associated molecular patterns.41–46Multiomic studies have demonstrated distinct pathophysiological alterations in adult and pediatric patients.47Plasma from critically ill adults with COVID-19 induced fibrinogen-dependent red blood cell aggregation and damaged the endothelial glycocalyx, resulting in an increased potential for microvascular thrombi formation. In contrast, pediatric patients demonstrated proinflammatory cytokine upregulation, including complement and coagulation cascade alterations, resulting in immune dysregulation and a hyperinflammatory state. Nevertheless, we were unable to establish causation in this retrospective study. Although none of the patients in this series had an active SARS-CoV-2 infection at the time of presentation, we were limited in our ability to test for a previous infection. The relationship between COVID-19 and a subsequent predisposition to thromboembolic complications is an important area for future study.
Limitations
This study has several limitations. Of note, septic CVST has frequently been documented in the presence of sinusitis or mastoiditis without a concomitant intracranial epidural abscess or subdural empyema. Nevertheless, the objective of this study was to investigate the management of septic CVST following a neurosurgical intervention; therefore, the inclusion criteria were limited to patients with a sinogenic or otogenic intracranial infection who underwent a neurosurgical procedure. Consequently, the narrower scope resulted in a smaller sample size. Although this study included patients from 3 centers in geographically disparate locations (East Coast, Midwest, and West Coast), expanding the study to other centers may improve the generalizability of the findings and the power of the statistical analyses. Additionally, the study is limited by its retrospective nature. In particular, patients’ vaccination history and the presence of a recent viral infection (including COVID-19) were rarely documented in the medical record. Therefore, it is not possible to derive mechanistic insights from these data. Patients were also treated with a variety of anticoagulation paradigms, complicating the ability to comment on the safety and efficacy of one particular treatment regimen. Finally, additional follow-up is necessary to determine long-term clinical and radiological outcomes.
Conclusions
败血性CVST pediatr中经常被发现ic patients with sinogenic and/or otogenic intracranial infections. Hydration, surgical intervention, and broad-spectrum parenteral antibiotics with good penetration of the blood-brain barrier remain key elements of the acute management of these patients, but the role of anticoagulation remains controversial because of the concern for hemorrhagic complications. In this multicenter series, we provide preliminary evidence that anticoagulation can be used safely in the acute postoperative period, but recommend that it be administered cautiously, in an appropriately monitored setting, and with interval cross-sectional imaging. Some patients exhibit excellent outcomes without anticoagulation, and further studies are needed to identify those patients who may benefit the most from anticoagulation.
Disclaimer
The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the U.S. Government.
版权声明:Ravindra博士说,“我是一个military Service member. This work was prepared as part of my official duties. Title 17, U.S.C., §105 provides that copyright protection under this title is not available for any work of the U.S. Government. Title 17, U.S.C., §101 defines a U.S. Government work as a work prepared by a military Service member or employee of the U.S. Government as part of that person’s official duties."
Disclosures
The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
Author Contributions
Conception and design: Hersh. Acquisition of data: Sutter, Anderson, Sahyouni, Plonsker, Ravindra, Gonda, Dziugan, Votoupal, DeCuypere, Angelo, Halloran. Analysis and interpretation of data: Hersh, Sutter, Anderson, Ravindra, Gonda, Levy, DeCuypere, Angelo, Michelow, McKay. Drafting the article: Hersh, Sutter, Anderson, Leclair, Angelo, Halloran. Critically revising the article: Hersh, Sutter, Anderson, Ravindra, DeCuypere, Angelo, Martin, Bookland, Michelow, McKay. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Hersh. Statistical analysis: Anderson. Administrative/technical/material support: Anderson, Martin. Study supervision: Hersh.
Supplemental Information
Videos
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8 ↑
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9 ↑
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10 ↑
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11 ↑
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12 ↑
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13 ↑
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14 ↑
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15 ↑
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16 ↑
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17 ↑
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19 ↑
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20 ↑
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21 ↑
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22 ↑
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23 ↑
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24 ↑
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25 ↑
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26 ↑
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28 ↑
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29 ↑
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31 ↑
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32 ↑
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33 ↑
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35 ↑
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41 ↑
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46 ↑
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47 ↑
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