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Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Otogenic lateral sinus thrombosis: Case series and controversies Jamie L. Funamura a,*, Alexander T. Nguyen b,1, Rodney C. Diaz a,1 a b
Department of Otolaryngology, University of California Davis Medical Center, United States University of California Davis School of Medicine, United States
A R T I C L E I N F O
A B S T R A C T
Article history: Received 7 December 2013 Received in revised form 1 February 2014 Accepted 3 March 2014 Available online xxx
Objectives: The aim of this study is to (1) report the clinical presentation, treatment, and sequelae in a series of pediatric patients with otogenic lateral sinus thrombosis and (2) to review the most controversial aspects of management of this rare intracranial complication of otitis media. Methods: Retrospective chart review of inpatients treated for central venous thrombosis at a tertiary care facility between 1996 and 2012. Results: Five pediatric patients (four male, one female) were identified with otogenic lateral sinus thrombosis. Age at presentation ranged from 13 months to 15 years. All underwent a surgical procedure, ranging from a simple myringotomy with tympanostomy tube placement to tympanomastoidectomy and internal jugular vein ligation or craniotomy. Three were anticoagulated with unfractionated heparin with subsequent transition to low molecular weight heparin of variable duration. One patient developed a non-life-threatening intracranial hemorrhage while on long-term anticoagulation. Follow-up imaging, when available, did not directly correlate complete thrombus resolution with use of anticoagulation or with persistent symptoms. Conclusions: Otogenic lateral sinus thrombosis is a rare intracranial complication of otitis media with significantly reduced morbidity and mortality in the modern era of antibiotic treatment, surgical intervention, and anticoagulation therapy. Due to the rarity of this condition today, the recommended extent of surgical intervention and need for routine anticoagulation are unclear, and requires further data to determine definitively. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Otomastoiditis Lateral sinus thrombosis Anticoagulation Acute otitis media Intracranial Complications
1. Introduction Lateral sinus thrombosis is a known, but increasingly more rare intracranial complication of otitis media. The term lateral sinus thrombosis refers to thrombus formation in the sigmoid and/or transverse sinus, which may extend to the jugular bulb and internal jugular vein. Thrombosis or thrombophlebitis may arise either from direct extension of the middle ear or mastoid, or through hematogenous spread via emissary veins. Associated and resultant complications include intracranial abscess or meningitis, septic thrombi to the systemic circulation, or interference with normal CSF resorption by the thrombus itself, resulting in otitic hydrocephalus [1]. Lateral sinus thrombosis can occur as the result
* Corresponding author at: 2521 Stockton Boulevard, Suite 7200, Sacramento, CA 95817, United States. Tel.: +1 916 734 2801. E-mail address: [email protected] (J.L. Funamura). 1 2521 Stockton Boulevard, Suite 7200, Sacramento, CA 95817, United States.
of noninfectious causes in both children and adults, but an infectious etiology – specifically that of middle ear and mastoid disease – in the pediatric population is the focus of this study. The classic presentation of otogenic lateral sinus thrombosis in the pre-antibiotic era is that of high-spiking or ‘‘picket-fence’’ fevers, headache, papilledema, and malaise. These occur in conjunction with a history of acute or chronic middle ear disease and otorrhea, otalgia, hearing loss, or edema and tenderness over the mastoid known as the Griesenger sign [2,3]. It has been noted that the classic signs and symptoms of middle ear infection may be masked by early antibiotic therapy, and therefore require a higher degree of suspicion in order to proceed with the appropriate workup [3]. Magnetic resonance venography (MRV) is considered the diagnostic imaging modality of choice, while contrast-enhanced computed tomography (CT) is less sensitive but can provide helpful corollary information [2–7]. Lateral sinus thrombosis is currently treated with intravenous antibiotics and surgical intervention with or without anticoagulation. Traditional surgical interventions include tympanomastoidectomy,
http://dx.doi.org/10.1016/j.ijporl.2014.03.002 0165-5876/ß 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: J.L. Funamura, et al., Otogenic lateral sinus thrombosis: Case series and controversies, Int. J. Pediatr. Otorhinolaryngol. (2014), http://dx.doi.org/10.1016/j.ijporl.2014.03.002
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needle aspiration or thrombus evacuation from the sigmoid sinus, and occasionally internal jugular vein ligation. In the pre-antibiotic era, the estimated mortality of the condition was 100% in patients who did not undergo surgery versus 20% for surgically treated cases [8]. Combining surgical management with parenteral antibiotics – and in many cases, anticoagulation – has significantly improved outcomes in patients with lateral sinus thrombosis. Mortality is now thought to be less than 1% [1,9,10]. Due to the rarity of lateral sinus thrombosis in the era of widespread antibiotic use, controversies persist as to what constitutes the most appropriate surgical and medical management. While most surgeons will perform a mastoidectomy with or without myringotomy tube placement and sinus aspiration, treatment of the thrombus after confirming absent blood flow with a dry aspiration ranges from no further intervention to venotomy and thrombectomy. More controversial than surgical intervention, however, is the role of routine anticoagulation in the management of lateral sinus thrombosis. Proponents of anticoagulant therapy cite its efficacy in preventing embolization or persistent septic thrombi, relative safety, evidence of recanalization on follow-up imaging, and possible reduction of neurologic sequelae [3,11,12]. Other authors caution against the routine use of anticoagulants due to hemorrhagic complications, evidence of recanalization without anticoagulation, and clinical recovery despite persistent thrombus [7,13]. The goal of our study was to review the presentation, management, and clinical sequelae of pediatric patients treated for lateral sinus thrombosis at our institution. In doing so, we aim to add to the existing data as well as highlight the controversial aspects in management of this now rare intracranial complication of otitis media. 2. Methods A retrospective chart review was performed of all patients treated for otogenic lateral sinus thrombosis at the UC Davis Medical Center from July 1996 to July 2012. Patients were identified based on a search of patients in the UC Davis Health System with the assistance of the Professional Billing Group. Patients were identified by the ICD-9 codes 325 (phlebitis and thrombophlebitis of intracranial venous sinuses) and 437.6 (intracranial venous sinus thrombosis). A total of 129 patients were identified by these methods. The medical records of these patients were then reviewed in order to identify all cases of lateral sinus thrombosis of an otogenic origin. Inclusion criteria included patients with a preceding or synchronous diagnosis of acute otitis media or otomastoiditis in conjunction with an intracranial sinus thrombosis on the affected side. Patients with history of preceding trauma or aseptic hypercoagulable states (e.g. neoplasm, postpartum), and those over the age of 18 were excluded. Six patients were identified as having an otogenic lateral sinus thrombosis, five of whom were under the age of 18. These charts were then thoroughly reviewed for patient demographic information, length of hospital stay, final diagnoses, surgical and medical interventions, diagnostic and follow-up imaging results, and clinical sequelae. Partial resolution of thrombus was identified by present but reduced flow through the previous thrombosed segments and/or visualization of residual thrombus, with complete resolution being resumption of normal flow and/or no evidence of thrombus. Anticoagulation, when administered, consisted of initiation with an unfractionated heparin drip with ultimate transition to long-term low molecular weight heparin (enoxaparin). This study was approved by the Institutional Review Board at the University of California Davis Medical Center (389556-1).
3. Results Five patients under the age of 18 were treated at our institution for otogenic lateral sinus thrombosis. Characteristics and presentation are demonstrated in Table 1. Fever was a presenting symptom in all patients, with only one demonstrating the classic spiking fever. Otologic signs and symptoms such as otalgia, otorrhea, and mastoid tenderness were variable. Positive otoscopy findings, when available, included purulence, middle ear effusions, and a retraction pocket with keratin debris. Neurologic findings such as headache, facial nerve palsy, nausea/vomiting, and seizure were also variable but more prominent than might be expected in uncomplicated acute otitis media. Patient demographics, diagnoses, medical/surgical treatment, and outcomes are shown in Table 2. Age at presentation ranged from 13 months to 15 years of age. Final diagnoses ranged from isolated otomastoiditis with lateral sinus thrombosis to suspected septic pulmonary emboli. One patient was found to have cholesteatoma at the time of surgery. Of note, four out of five patients presented with a second intracranial complication of otitis media (in addition to lateral sinus thrombosis): patient 1 with meningitis, patients 2–4 with epidural abscesses, and patient 3 with delayed brain abscess. Otitic hydrocephalus was not diagnosed in any of the patients in our case series. In all cases, the initial diagnosis was suspected or made by head CT and later confirmed by MRV Fig. 1. Surgical intervention in our patients ranged from simple tympanostomy tube placement to more extensive procedures depending on the clinical picture. Patient 5, who underwent tympanostomy tube placement alone, was asymptomatic without fever or leukocytosis and had been treated with multiple doses of intramuscular and intravenous antibiotics prior to presentation. This patient had no bacterial growth from his ear aspirate; all other patients had positive cultures. All other patients also had more advanced disease at the time of presentation and underwent mastoidectomy with sinus aspiration. No thrombectomies were performed as no purulent material was aspirated intraoperatively. Patient 2 also underwent internal jugular (IJ) vein ligation later during his hospitalization due to concerns for septic pulmonary emboli based on chest radiography with ventilator dependence and septicemia. Patient 3 underwent a craniectomy with drainage of a brain abscess that developed 1 week after initial mastoidectomy and drainage of an epidural abscess. Earlier in our series (patients 1 and 2), no anticoagulation was used in the treatment of lateral sinus thrombosis. Patient 1 did not undergo follow-up imaging, but patient 2 demonstrated at least partial thrombus resolution on MRV. He had also undergone IJ ligation but had evidence of some flow in this area, possibly due to development of collateral circulation. Patients 3–5 were treated with unfractionated heparin and subsequent transition to enoxaparin at the recommendation of the pediatric hematology, neurology, or neurosurgery services who favor anticoagulation at our institution. Patient 3 was initially thought to develop a significant intracranial hemorrhage as a result of anticoagulation, Table 1 Patient symptoms and clinical findings on presentation. Symptoms
n
%
Clinical findings
n
%
Otalgia Headache Anorexia Nausea/vomiting
3 3 3 2
60 60 60 40
5 1 2 1
100 20 40 20
Lethargy/malaise Neck pain Rhinorrhea
2 1 2
40 20 40
Fever Spiking fevers Otorrhea Mastoid tenderness/ erythema/edema Facial nerve palsy Seizure Positive cultures
1 1 4
20 20 80
Please cite this article in press as: J.L. Funamura, et al., Otogenic lateral sinus thrombosis: Case series and controversies, Int. J. Pediatr. Otorhinolaryngol. (2014), http://dx.doi.org/10.1016/j.ijporl.2014.03.002
Age
Gender
Duration of symptoms (prior to presentation)
Otoscopy findings
Diagnoses
Thrombus location (diagnostic modality)
Surgical intervention
1 2
13 months 15 years
M M
2 days 7 days
Bulging, erythematous TMs (bilateral) Posterior-superior retraction pocket, extensive keratin debris (left)
Right SS (head CT, confirmed by MRV) Left TS, SS (head CT, confirmed with sinus aspiration, later by MRV)
Mastoidectomy (1) Mastoidectomy, drainage of epidural abscess; (2) IJ ligation
3
8 years
F
3 weeks
Copious otorrhea (left)
Right otomastoiditis, meningitis Left otomastoiditis, epidural abscess, cholesteatoma, suspected septic pulmonary emboli Left otomastoiditis, epidural and brain abscesses
Left TS, SS, IJ (head CT, confirmed by MRV)
4
19 months
M
4 days
Unknown
5
5 years
M
6 days
Non-bulging TM with middle ear effusion
Left otomastoiditis, subperiosteal and epidural abscesses Right otomastoiditis
Left TS, SS, jugular bulb (head CT, confirmed by MRV) Right TS, SS, proximal IJ (head CT, confirmed by MRV)
(1) Mastoidectomy, tympanostomy tube, drainage of epidural abscess; (2) craniotomy with drainage of brain abscess Mastoidectomy, drainage of epidural and subperiosteal abscesses Myringotomy with tympanostomy tube
Pt Sinus management
Antibiotics: prior to dx; after dx (duration)
Microbiology (source)
Anticoagulation (duration/monitoring)
Length of stay (days) Follow-up MR
1
Dry aspiration
Haemophilus influenza (CSF)
None
30
N/A
2
Dry aspiration
None; ampicillin, cefotaxime, ceftazidime, clindamycin (22 days) Yes – unknown (1 day); ceftriaxone, metronidazole (4 weeks)
None
10
Partial resolution of thrombus on MRV with partial recanalization versus collateral flow
1 month
3
Bloody aspiration Yes – penicillin (3 weeks); ceftriaxone (6 weeks)
Corynebacterium spp., (ear aspirate); Bacteroides fragilis, Peptostreptococcus spp., Escherichia coli (sub-periosteal abscess) Streptococcus anginosus (ear swab)
Epilepsy, developmental delay None
61
Complete resolution of thrombus on MRV
5 months
Headache
4
Bloody aspiration Yes – ceftriaxone (3 days); ceftriaxone, cefotaxime, clindamycin (7 days), amoxicillinclavulanate (3 weeks) None Yes – ceftriaxone and clindamycin (2 days); ceftriaxone, piperacillintazobactam (7 days), amoxicillinclavulanate (3 weeks)
Heparin (3 weeks – aPTT), enoxaparin (3 months – anti-Xa, stopped due to ICH) Heparin (3 days – aPTT), enoxaparin (6 months – anti-Xa)
9
Partial resolution of thrombus on MRI
3 months
None
7
Complete resolution of thrombus on MRV
3 months
None
5
Streptococcus viridans (unknown)
No bacterial growth (ear aspirate)
Heparin (3 days – aPTT), enoxaparin (3 months – anti-Xa)
MR interval (months) Clinical sequelae
Abbreviations: SS – sigmoid sinus, TS – transverse sinus, IJ – internal jugular vein, ICH – intracranial hemorrhage, MRV – magnetic resonance venography, TM – tympanic membrane, aPTT – activated partial thromboplastin time.
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Please cite this article in press as: J.L. Funamura, et al., Otogenic lateral sinus thrombosis: Case series and controversies, Int. J. Pediatr. Otorhinolaryngol. (2014), http://dx.doi.org/10.1016/j.ijporl.2014.03.002
Table 2 Patient characteristics, treatment, and outcome data.
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Fig. 1. MRV of patient 4 with thrombus of left transverse sinus, sigmoid sinus, and jugular bulb.
but found intraoperatively to have a large brain abscess without hemorrhagic component. She did, however, later develop a small intracranial hemorrhage as an outpatient and enoxaparin was subsequently discontinued 3 months into therapy. Chart review revealed that she was receiving a subcutaneous dose greater than the recommended 1 mg/kg for every 12 h at the time of this incident (1.6 mg/kg for every 12 h). However, her anti-factor Xa level was in the therapeutic range on all preceding heparin assays at this dose, the most recent being 2 weeks prior. No MRV was obtained at this time, but MRV at 5 months following initial diagnosis demonstrated complete thrombus resolution. Patient 4 was shown to have incomplete thrombus resolution at 3 months and was continued on enoxaparin for 6 months total although no subsequent imaging was available. Patient 5 had complete resolution of thrombus on MRV at 3 months and enoxaparin was discontinued at this time. While being treated with unfractionated heparin, patients were monitored with activated partial thromboplastin time (aPTT). Patients receiving enoxaparin underwent anti-factor Xa level monitoring with a goal range between 0.5 and 1 units/mL. Clinical sequelae were significant for two patients. Patient 1, who presented with meningitis and seizures, is developmentally delayed with epilepsy. Patient 3, who developed a brain abscess, had a significantly longer recovery period and persistent headache but is otherwise doing well. Patients 2, 4, and 5 showed no longterm sequelae from their disease but also had much shorter hospitalizations (7–10 days compared to 1–2 months).
4. Discussion Otogenic lateral sinus thrombosis is now an infrequently encountered complication of acute otitis media. Advances in antibiotic therapy, temporal bone surgery, and magnetic resonance imaging have greatly reduced both the incidence and the resultant morbidity of the disease. While this is a triumph for modern medicine, the rarity of lateral sinus thrombosis and the even more rare occurrence of poor outcomes now present a treatment dilemma. The extent of surgical intervention and routine use of anticoagulation are two components of the management of lateral sinus thrombosis with which the most controversy exists.
Routine surgical intervention for otogenic lateral sinus thrombosis typically consists of cortical mastoidectomy with or without myringotomy tube placement and with or without sinus aspiration [7,10]. A modified radical mastoidectomy may be warranted if extensive cholesteatoma is present. Internal jugular vein ligation is not routinely recommended, but is performed when persistent septicemia or septic pulmonary emboli occur, as with one of our patients. Recent case series have reported excellent outcomes in select patients with myringotomy or medical therapy alone [7,12,14], as was our experience. Certainly most patients, however, will warrant a mastoidectomy at the time of diagnosis. Au et al. found that 94.2% of all patients diagnosed with lateral sinus thrombosis underwent mastoid surgery in their review of the literature over the past 20 years [10]. Mastoidectomy is particularly applicable in a patient with a history of chronic otitis media in whom a cholesteatoma may be present, and when there is evidence of an advanced or aggressive infection. Our other patients presented with a second intracranial complication (meningitis, epidural abscess) at the time of diagnosis that merited a more aggressive surgical intervention. Management of the affected sinus varies greatly in the literature. Mastoidectomy is thought to remove perisinus infection and granulation tissue, thereby reducing the thrombophilic nidus. Whether needle aspiration to confirm diagnosis or rule out a purulent thrombophlebitis is necessary and if subsequent thrombectomy alters disease progression is contested. In the same 20year review, Au et al. found that 54.9% of patients underwent needle aspiration and 47.1% thrombectomy, but the outcomes in these patients could not demonstrate superior efficacy of either treatment [10]. None of our patients underwent thrombectomy, but as mentioned above, one patient underwent IJ ligation for presumed septic pulmonary emboli. A significant benefit on the added utility of anticoagulant therapy has also yet to be definitely demonstrated in the current literature. Neilan et al. pooled data from eight studies for type of treatment and recanalization by follow-up imaging. Their group found that 20 out of 30 (66.7%) patients who were anticoagulated showed evidence of recanalization compared to 9 out of 17 (52.9%) who were not anticoagulated (P = 0.53) [15]. Limiting their review to the last 20 years, Au et al. reported 16 out of 19 (84%) anticoagulated patients and three of four (75%) non-anticoagulated patients demonstrated at least partial recanalization. Thirty-two out of 41 (78.6%) patients showed at least partial recanalization overall [10]. These numbers do suggest a trend toward an added benefit of anticoagulation, but lack the statistical power to draw definitive conclusions. If anticoagulation does increase the likelihood of at least partial recanalization following treatment, the next question is how the presence of recanalization translates to clinical significance in terms of symptom resolution or avoidance of neurological sequelae. In the case series presented by Sitton et al., five out of seven patients were asymptomatic at the time of discharge, one with no change in radiographic appearance several months later. Another patient had resolution of symptoms several months before imaging confirmed resolution, and another with persistent symptoms despite resolution on imaging 1 month after original diagnosis [7]. The difficulty in attributing significance to the use of anticoagulation in preventing neurologic sequelae is reinforced in our own experience. Two of our patients developed persistent symptoms. The first (Patient 1) was not treated with anticoagulation, while the second (Patient 3) did was treated with a 3 month course of anticoagulation. However, our first patient was the only patient with an initial diagnosis of meningitis, and his hospital course was complicated by intractable seizures, with clinical sequelae of epilepsy and developmental delay. The other patient developed a brain abscess and required multiple
Please cite this article in press as: J.L. Funamura, et al., Otogenic lateral sinus thrombosis: Case series and controversies, Int. J. Pediatr. Otorhinolaryngol. (2014), http://dx.doi.org/10.1016/j.ijporl.2014.03.002
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craniotomy procedures, each of which are independent risk factors for headache. We therefore have both examples of neurologic sequelae in both patients treated with and without anticoagulation with significant confounding factors within our own limited study. Another factor that may temper enthusiasm for routine use of anticoagulants in the management of lateral sinus thrombosis is the prospect of anticoagulation-related complications. Shah et al. reported two cases of post-operative hemorrhage related to low molecular weight heparin (enoxaparin, 1 mg/kg subcutaneously for every 12 h) [13]. Ropposch et al., on the other hand, presented a case series in which six patients were treated with low molecular weight heparin (enoxaparin, 1 mg/kg subcutaneously once a day) for 3 months after initial unfractionated heparin administration for 3 days post-operatively. Intermittent activated partial thromboplastin (aPTT) time and anti-factor Xa plasma levels were monitored, and no anticoagulant-related complications were evident. All patients had evidence of recanalization at 3 months, and the authors concluded that low molecular weight heparin is a safe treatment option when administered correctly [11]. In our series, we had an anticoagulant-related intracranial hemorrhage that did not require surgical intervention but resulted in early discontinuation of low molecular weight heparin (enoxaparin, 1.6 mg/kg subcutaneously every 12 h with normal anti-factor Xa levels). Low molecular weight heparin (enoxaparin) that is now a favored agent for long-term anticoagulation due to more predictable inhibition of coagulation enzymes resulting in the ability to administer fixed weight-adjusted doses without laboratory monitoring [11]. Enoxaparin is FDA-approved for treatment of thromboembolism at doses of 1 mg/kg subcutaneously every 12 h in patients greater than 2 months of age, and at 1.5 mg/kg in patients under 2 months of age. Efficacy and safety of enoxaparin in neonates and children has not been well-studied and therefore titration to effect of anti-factor Xa level of 0.5–1.0 U/mL 4–6 h postinjection is recommended [11,16]. Anticoagulation safety and efficacy have not been extensively studied in pediatric populations. Literature from other pediatric neurology and hematology literature was examined for prospective studies addressing this issue. In a recent and rare prospective study with a relatively large number of subjects, Moharir et al. followed pediatric patients with cerebral sinus thrombosis from all causes to measure bleeding complication and thrombus propagation with anticoagulation. Patients underwent pre- and postanticoagulation neuroimaging and monitored for major hemorrhagic events (hemoglobin drop >2 g/dL or requiring blood transfusion). Six percent (6/99) of anticoagulated patients had a major hemorrhagic event; all non-fatal and associated with comparable clinical outcomes as those without hemorrhage event. However, thrombus propagation was noted in 7/19 (38%) of children treated without, versus 3/44 (7%) treated with anticoagulation (p = 0.006), with worse clinical outcomes. These results led authors to state that anticoagulation appears safe in children with cerebral sinus thrombosis and merit strong consideration in treatment to improve clinical outcomes [16]. The state of current evidence suggests that the routine use of anticoagulation is not definitively supported based on a paucity of strong evidence for an independent or additive role in the treatment of lateral sinus thrombosis [10,15]. Anticoagulant therapy, however, has been shown to be generally safe in young
5
children with proper monitoring [11,16]. Because rare anticoagulant-related complications will occur despite appropriate dosing and monitoring, the clinician must weigh this risk with the potential benefit of preventing thrombus propagation and improved clinical outcome [12,13,16]. Additional data will need to be collected in order to further guide clinicians in making this choice. Given the rarity of the condition and its potential for morbidity or mortality, we are currently reliant upon data collected via case series of experiences from individual institutions. Ongoing reports of medical and surgical therapy as well as outcome should therefore be encouraged to build an evidencebased management strategy of this rare intracranial complication of otitis media.
5. Conclusion The extent of surgery and the role of anticoagulation in the treatment of otogenic lateral sinus thrombosis are two major controversies that have yet to be resolved. Further data will be necessary in order to provide adequate evidence-based guidelines for the routine management of lateral sinus thrombosis.
References [1] C.D. Bluestone, J.O. Klein, Intracranial complications of otitis media and mastoiditis, in: C.D. Bluestone, et al. (Eds.), Pediatric Otolaryngology, 4th ed., Saunders, Philadelphia, 2003, pp. 772–774. [2] I. Bielecki, M. Cofala, J. Mierzwinski, Otogenic lateral sinus thrombosis in children, Otol. Neurotol. 32 (2011) 1111–1115. [3] C.B. Bales, S. Sobol, R. Wetmore, L.M. Elden, Lateral sinus thrombosis as a complication of otitis media: 10-year experience at the children’s hospital of Philadelphia, Pediatrics 123 (2009) 7009–7013. [4] N. Christensen, J. Wayman, J. Spencer, Lateral sinus thrombosis: a review of seven cases and proposal of a management algorithm, Int. J. Pediatr. Otorhinolaryngol. 73 (2009) 581–584. [5] K.E. Kelly, R.K. Jackler, W.P. Dillon, Diagnosis of septic sigmoid sinus thrombosis with magnetic resonance imaging, Otolaryngol. Head Neck Surg. 105 (1991) 617–624. [6] C. Virapongse, C. Cazenave, R. Quisling, M. Sarwar, S. Hunter, The empty delta sign: frequency and significance in 76 cases of dural sinus thrombosis, Radiology 162 (1987) 779–785. [7] M.S. Sitton, R. Chun, Pediatric otogenic lateral sinus thrombosis: role of anticoagulation and surgery, Int. J. Pediatr. Otorhinolaryngol. 76 (2012) 428–432. [8] G.E. Shambaugh, Jr., M.E. Glasscock (Eds.), Surgery of the Ear, Saunders, Philadelphia, 1980, pp. 302–309. [9] D.M. Kaplan, M. Kraus, M. Puterman, A. Niv, A. Leiberman, D.M. Fliss, Otogenic lateral sinus thrombosis in children, Int. J. Pediatr. Otorhinolaryngol. 49 (1999) 177–183. [10] J.K. Au, S.I. Adam, E.M. Michaelides, Contemporary management of pediatric lateral sinus thrombosis: a twenty year review, Am. J. Otolaryngol. 34 (2013) 145–150. [11] T. Ropposch, U. Nemetz, E.M. Braun, A. Lackner, C. Walch, Low molecular weight heparin therapy in pediatric otogenic sigmoid sinus thrombosis: a safe treatment option, Int. J. Pediatr. Otorhinolaryngol. 76 (2012) 1023–1026. [12] E. Novoa, M. Podvinec, R. Angst, N. Gurtler, Paediatric otogenic lateral sinus thrombosis: therapeutic management, outcome, and thrombophilic evaluation, Int. J. Pediatr. Otorhinolaryngol. 77 (2013) 996–1001. [13] U.K. Shah, T.F. Jubelirer, J.D. Fish, L.M. Elden, A caution regarding the use of lowmolecular weight heparin in pediatric otogenic lateral sinus thrombosis, Int. J. Pediatr. Otorhinolaryngol. 71 (2007) 347–351. [14] E.E. Tov, A. Leiberman, I. Shelef, D.M. Kaplan, Conservative nonsurgical treatment of a child with otogenic lateral sinus thrombosis, Am. J. Otolaryngol. 29 (2008) 138–141. [15] R.E. Neilan, B. Isaacson, J.W. Kutz Jr., K. Lee, P.S. Roland, Pediatric otogenic lateral sinus thrombosis recanalization, Int. J. Pediatr. Otorhinolaryngol. 75 (2011) 850– 853. [16] M.D. Moharir, M. Shroff, D. Stephens, A.M. Pontigon, A. Chan, D. MacGregor, et al., Anticoagulants in pediatric cerebral sinovenous thrombosis: a safety and outcome study, Ann. Neurol. 67 (2010) 590–599.
Please cite this article in press as: J.L. Funamura, et al., Otogenic lateral sinus thrombosis: Case series and controversies, Int. J. Pediatr. Otorhinolaryngol. (2014), http://dx.doi.org/10.1016/j.ijporl.2014.03.002
PEDOT-7031; No. of Pages 5 International Journal of Pediatric Otorhinolaryngology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Otogenic lateral sinus thrombosis: Case series and controversies Jamie L. Funamura a,*, Alexander T. Nguyen b,1, Rodney C. Diaz a,1 a b
Department of Otolaryngology, University of California Davis Medical Center, United States University of California Davis School of Medicine, United States
A R T I C L E I N F O
A B S T R A C T
Article history: Received 7 December 2013 Received in revised form 1 February 2014 Accepted 3 March 2014 Available online xxx
Objectives: The aim of this study is to (1) report the clinical presentation, treatment, and sequelae in a series of pediatric patients with otogenic lateral sinus thrombosis and (2) to review the most controversial aspects of management of this rare intracranial complication of otitis media. Methods: Retrospective chart review of inpatients treated for central venous thrombosis at a tertiary care facility between 1996 and 2012. Results: Five pediatric patients (four male, one female) were identified with otogenic lateral sinus thrombosis. Age at presentation ranged from 13 months to 15 years. All underwent a surgical procedure, ranging from a simple myringotomy with tympanostomy tube placement to tympanomastoidectomy and internal jugular vein ligation or craniotomy. Three were anticoagulated with unfractionated heparin with subsequent transition to low molecular weight heparin of variable duration. One patient developed a non-life-threatening intracranial hemorrhage while on long-term anticoagulation. Follow-up imaging, when available, did not directly correlate complete thrombus resolution with use of anticoagulation or with persistent symptoms. Conclusions: Otogenic lateral sinus thrombosis is a rare intracranial complication of otitis media with significantly reduced morbidity and mortality in the modern era of antibiotic treatment, surgical intervention, and anticoagulation therapy. Due to the rarity of this condition today, the recommended extent of surgical intervention and need for routine anticoagulation are unclear, and requires further data to determine definitively. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Otomastoiditis Lateral sinus thrombosis Anticoagulation Acute otitis media Intracranial Complications
1. Introduction Lateral sinus thrombosis is a known, but increasingly more rare intracranial complication of otitis media. The term lateral sinus thrombosis refers to thrombus formation in the sigmoid and/or transverse sinus, which may extend to the jugular bulb and internal jugular vein. Thrombosis or thrombophlebitis may arise either from direct extension of the middle ear or mastoid, or through hematogenous spread via emissary veins. Associated and resultant complications include intracranial abscess or meningitis, septic thrombi to the systemic circulation, or interference with normal CSF resorption by the thrombus itself, resulting in otitic hydrocephalus [1]. Lateral sinus thrombosis can occur as the result
* Corresponding author at: 2521 Stockton Boulevard, Suite 7200, Sacramento, CA 95817, United States. Tel.: +1 916 734 2801. E-mail address: [email protected] (J.L. Funamura). 1 2521 Stockton Boulevard, Suite 7200, Sacramento, CA 95817, United States.
of noninfectious causes in both children and adults, but an infectious etiology – specifically that of middle ear and mastoid disease – in the pediatric population is the focus of this study. The classic presentation of otogenic lateral sinus thrombosis in the pre-antibiotic era is that of high-spiking or ‘‘picket-fence’’ fevers, headache, papilledema, and malaise. These occur in conjunction with a history of acute or chronic middle ear disease and otorrhea, otalgia, hearing loss, or edema and tenderness over the mastoid known as the Griesenger sign [2,3]. It has been noted that the classic signs and symptoms of middle ear infection may be masked by early antibiotic therapy, and therefore require a higher degree of suspicion in order to proceed with the appropriate workup [3]. Magnetic resonance venography (MRV) is considered the diagnostic imaging modality of choice, while contrast-enhanced computed tomography (CT) is less sensitive but can provide helpful corollary information [2–7]. Lateral sinus thrombosis is currently treated with intravenous antibiotics and surgical intervention with or without anticoagulation. Traditional surgical interventions include tympanomastoidectomy,
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Please cite this article in press as: J.L. Funamura, et al., Otogenic lateral sinus thrombosis: Case series and controversies, Int. J. Pediatr. Otorhinolaryngol. (2014), http://dx.doi.org/10.1016/j.ijporl.2014.03.002
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needle aspiration or thrombus evacuation from the sigmoid sinus, and occasionally internal jugular vein ligation. In the pre-antibiotic era, the estimated mortality of the condition was 100% in patients who did not undergo surgery versus 20% for surgically treated cases [8]. Combining surgical management with parenteral antibiotics – and in many cases, anticoagulation – has significantly improved outcomes in patients with lateral sinus thrombosis. Mortality is now thought to be less than 1% [1,9,10]. Due to the rarity of lateral sinus thrombosis in the era of widespread antibiotic use, controversies persist as to what constitutes the most appropriate surgical and medical management. While most surgeons will perform a mastoidectomy with or without myringotomy tube placement and sinus aspiration, treatment of the thrombus after confirming absent blood flow with a dry aspiration ranges from no further intervention to venotomy and thrombectomy. More controversial than surgical intervention, however, is the role of routine anticoagulation in the management of lateral sinus thrombosis. Proponents of anticoagulant therapy cite its efficacy in preventing embolization or persistent septic thrombi, relative safety, evidence of recanalization on follow-up imaging, and possible reduction of neurologic sequelae [3,11,12]. Other authors caution against the routine use of anticoagulants due to hemorrhagic complications, evidence of recanalization without anticoagulation, and clinical recovery despite persistent thrombus [7,13]. The goal of our study was to review the presentation, management, and clinical sequelae of pediatric patients treated for lateral sinus thrombosis at our institution. In doing so, we aim to add to the existing data as well as highlight the controversial aspects in management of this now rare intracranial complication of otitis media. 2. Methods A retrospective chart review was performed of all patients treated for otogenic lateral sinus thrombosis at the UC Davis Medical Center from July 1996 to July 2012. Patients were identified based on a search of patients in the UC Davis Health System with the assistance of the Professional Billing Group. Patients were identified by the ICD-9 codes 325 (phlebitis and thrombophlebitis of intracranial venous sinuses) and 437.6 (intracranial venous sinus thrombosis). A total of 129 patients were identified by these methods. The medical records of these patients were then reviewed in order to identify all cases of lateral sinus thrombosis of an otogenic origin. Inclusion criteria included patients with a preceding or synchronous diagnosis of acute otitis media or otomastoiditis in conjunction with an intracranial sinus thrombosis on the affected side. Patients with history of preceding trauma or aseptic hypercoagulable states (e.g. neoplasm, postpartum), and those over the age of 18 were excluded. Six patients were identified as having an otogenic lateral sinus thrombosis, five of whom were under the age of 18. These charts were then thoroughly reviewed for patient demographic information, length of hospital stay, final diagnoses, surgical and medical interventions, diagnostic and follow-up imaging results, and clinical sequelae. Partial resolution of thrombus was identified by present but reduced flow through the previous thrombosed segments and/or visualization of residual thrombus, with complete resolution being resumption of normal flow and/or no evidence of thrombus. Anticoagulation, when administered, consisted of initiation with an unfractionated heparin drip with ultimate transition to long-term low molecular weight heparin (enoxaparin). This study was approved by the Institutional Review Board at the University of California Davis Medical Center (389556-1).
3. Results Five patients under the age of 18 were treated at our institution for otogenic lateral sinus thrombosis. Characteristics and presentation are demonstrated in Table 1. Fever was a presenting symptom in all patients, with only one demonstrating the classic spiking fever. Otologic signs and symptoms such as otalgia, otorrhea, and mastoid tenderness were variable. Positive otoscopy findings, when available, included purulence, middle ear effusions, and a retraction pocket with keratin debris. Neurologic findings such as headache, facial nerve palsy, nausea/vomiting, and seizure were also variable but more prominent than might be expected in uncomplicated acute otitis media. Patient demographics, diagnoses, medical/surgical treatment, and outcomes are shown in Table 2. Age at presentation ranged from 13 months to 15 years of age. Final diagnoses ranged from isolated otomastoiditis with lateral sinus thrombosis to suspected septic pulmonary emboli. One patient was found to have cholesteatoma at the time of surgery. Of note, four out of five patients presented with a second intracranial complication of otitis media (in addition to lateral sinus thrombosis): patient 1 with meningitis, patients 2–4 with epidural abscesses, and patient 3 with delayed brain abscess. Otitic hydrocephalus was not diagnosed in any of the patients in our case series. In all cases, the initial diagnosis was suspected or made by head CT and later confirmed by MRV Fig. 1. Surgical intervention in our patients ranged from simple tympanostomy tube placement to more extensive procedures depending on the clinical picture. Patient 5, who underwent tympanostomy tube placement alone, was asymptomatic without fever or leukocytosis and had been treated with multiple doses of intramuscular and intravenous antibiotics prior to presentation. This patient had no bacterial growth from his ear aspirate; all other patients had positive cultures. All other patients also had more advanced disease at the time of presentation and underwent mastoidectomy with sinus aspiration. No thrombectomies were performed as no purulent material was aspirated intraoperatively. Patient 2 also underwent internal jugular (IJ) vein ligation later during his hospitalization due to concerns for septic pulmonary emboli based on chest radiography with ventilator dependence and septicemia. Patient 3 underwent a craniectomy with drainage of a brain abscess that developed 1 week after initial mastoidectomy and drainage of an epidural abscess. Earlier in our series (patients 1 and 2), no anticoagulation was used in the treatment of lateral sinus thrombosis. Patient 1 did not undergo follow-up imaging, but patient 2 demonstrated at least partial thrombus resolution on MRV. He had also undergone IJ ligation but had evidence of some flow in this area, possibly due to development of collateral circulation. Patients 3–5 were treated with unfractionated heparin and subsequent transition to enoxaparin at the recommendation of the pediatric hematology, neurology, or neurosurgery services who favor anticoagulation at our institution. Patient 3 was initially thought to develop a significant intracranial hemorrhage as a result of anticoagulation, Table 1 Patient symptoms and clinical findings on presentation. Symptoms
n
%
Clinical findings
n
%
Otalgia Headache Anorexia Nausea/vomiting
3 3 3 2
60 60 60 40
5 1 2 1
100 20 40 20
Lethargy/malaise Neck pain Rhinorrhea
2 1 2
40 20 40
Fever Spiking fevers Otorrhea Mastoid tenderness/ erythema/edema Facial nerve palsy Seizure Positive cultures
1 1 4
20 20 80
Please cite this article in press as: J.L. Funamura, et al., Otogenic lateral sinus thrombosis: Case series and controversies, Int. J. Pediatr. Otorhinolaryngol. (2014), http://dx.doi.org/10.1016/j.ijporl.2014.03.002
Age
Gender
Duration of symptoms (prior to presentation)
Otoscopy findings
Diagnoses
Thrombus location (diagnostic modality)
Surgical intervention
1 2
13 months 15 years
M M
2 days 7 days
Bulging, erythematous TMs (bilateral) Posterior-superior retraction pocket, extensive keratin debris (left)
Right SS (head CT, confirmed by MRV) Left TS, SS (head CT, confirmed with sinus aspiration, later by MRV)
Mastoidectomy (1) Mastoidectomy, drainage of epidural abscess; (2) IJ ligation
3
8 years
F
3 weeks
Copious otorrhea (left)
Right otomastoiditis, meningitis Left otomastoiditis, epidural abscess, cholesteatoma, suspected septic pulmonary emboli Left otomastoiditis, epidural and brain abscesses
Left TS, SS, IJ (head CT, confirmed by MRV)
4
19 months
M
4 days
Unknown
5
5 years
M
6 days
Non-bulging TM with middle ear effusion
Left otomastoiditis, subperiosteal and epidural abscesses Right otomastoiditis
Left TS, SS, jugular bulb (head CT, confirmed by MRV) Right TS, SS, proximal IJ (head CT, confirmed by MRV)
(1) Mastoidectomy, tympanostomy tube, drainage of epidural abscess; (2) craniotomy with drainage of brain abscess Mastoidectomy, drainage of epidural and subperiosteal abscesses Myringotomy with tympanostomy tube
Pt Sinus management
Antibiotics: prior to dx; after dx (duration)
Microbiology (source)
Anticoagulation (duration/monitoring)
Length of stay (days) Follow-up MR
1
Dry aspiration
Haemophilus influenza (CSF)
None
30
N/A
2
Dry aspiration
None; ampicillin, cefotaxime, ceftazidime, clindamycin (22 days) Yes – unknown (1 day); ceftriaxone, metronidazole (4 weeks)
None
10
Partial resolution of thrombus on MRV with partial recanalization versus collateral flow
1 month
3
Bloody aspiration Yes – penicillin (3 weeks); ceftriaxone (6 weeks)
Corynebacterium spp., (ear aspirate); Bacteroides fragilis, Peptostreptococcus spp., Escherichia coli (sub-periosteal abscess) Streptococcus anginosus (ear swab)
Epilepsy, developmental delay None
61
Complete resolution of thrombus on MRV
5 months
Headache
4
Bloody aspiration Yes – ceftriaxone (3 days); ceftriaxone, cefotaxime, clindamycin (7 days), amoxicillinclavulanate (3 weeks) None Yes – ceftriaxone and clindamycin (2 days); ceftriaxone, piperacillintazobactam (7 days), amoxicillinclavulanate (3 weeks)
Heparin (3 weeks – aPTT), enoxaparin (3 months – anti-Xa, stopped due to ICH) Heparin (3 days – aPTT), enoxaparin (6 months – anti-Xa)
9
Partial resolution of thrombus on MRI
3 months
None
7
Complete resolution of thrombus on MRV
3 months
None
5
Streptococcus viridans (unknown)
No bacterial growth (ear aspirate)
Heparin (3 days – aPTT), enoxaparin (3 months – anti-Xa)
MR interval (months) Clinical sequelae
Abbreviations: SS – sigmoid sinus, TS – transverse sinus, IJ – internal jugular vein, ICH – intracranial hemorrhage, MRV – magnetic resonance venography, TM – tympanic membrane, aPTT – activated partial thromboplastin time.
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Please cite this article in press as: J.L. Funamura, et al., Otogenic lateral sinus thrombosis: Case series and controversies, Int. J. Pediatr. Otorhinolaryngol. (2014), http://dx.doi.org/10.1016/j.ijporl.2014.03.002
Table 2 Patient characteristics, treatment, and outcome data.
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Fig. 1. MRV of patient 4 with thrombus of left transverse sinus, sigmoid sinus, and jugular bulb.
but found intraoperatively to have a large brain abscess without hemorrhagic component. She did, however, later develop a small intracranial hemorrhage as an outpatient and enoxaparin was subsequently discontinued 3 months into therapy. Chart review revealed that she was receiving a subcutaneous dose greater than the recommended 1 mg/kg for every 12 h at the time of this incident (1.6 mg/kg for every 12 h). However, her anti-factor Xa level was in the therapeutic range on all preceding heparin assays at this dose, the most recent being 2 weeks prior. No MRV was obtained at this time, but MRV at 5 months following initial diagnosis demonstrated complete thrombus resolution. Patient 4 was shown to have incomplete thrombus resolution at 3 months and was continued on enoxaparin for 6 months total although no subsequent imaging was available. Patient 5 had complete resolution of thrombus on MRV at 3 months and enoxaparin was discontinued at this time. While being treated with unfractionated heparin, patients were monitored with activated partial thromboplastin time (aPTT). Patients receiving enoxaparin underwent anti-factor Xa level monitoring with a goal range between 0.5 and 1 units/mL. Clinical sequelae were significant for two patients. Patient 1, who presented with meningitis and seizures, is developmentally delayed with epilepsy. Patient 3, who developed a brain abscess, had a significantly longer recovery period and persistent headache but is otherwise doing well. Patients 2, 4, and 5 showed no longterm sequelae from their disease but also had much shorter hospitalizations (7–10 days compared to 1–2 months).
4. Discussion Otogenic lateral sinus thrombosis is now an infrequently encountered complication of acute otitis media. Advances in antibiotic therapy, temporal bone surgery, and magnetic resonance imaging have greatly reduced both the incidence and the resultant morbidity of the disease. While this is a triumph for modern medicine, the rarity of lateral sinus thrombosis and the even more rare occurrence of poor outcomes now present a treatment dilemma. The extent of surgical intervention and routine use of anticoagulation are two components of the management of lateral sinus thrombosis with which the most controversy exists.
Routine surgical intervention for otogenic lateral sinus thrombosis typically consists of cortical mastoidectomy with or without myringotomy tube placement and with or without sinus aspiration [7,10]. A modified radical mastoidectomy may be warranted if extensive cholesteatoma is present. Internal jugular vein ligation is not routinely recommended, but is performed when persistent septicemia or septic pulmonary emboli occur, as with one of our patients. Recent case series have reported excellent outcomes in select patients with myringotomy or medical therapy alone [7,12,14], as was our experience. Certainly most patients, however, will warrant a mastoidectomy at the time of diagnosis. Au et al. found that 94.2% of all patients diagnosed with lateral sinus thrombosis underwent mastoid surgery in their review of the literature over the past 20 years [10]. Mastoidectomy is particularly applicable in a patient with a history of chronic otitis media in whom a cholesteatoma may be present, and when there is evidence of an advanced or aggressive infection. Our other patients presented with a second intracranial complication (meningitis, epidural abscess) at the time of diagnosis that merited a more aggressive surgical intervention. Management of the affected sinus varies greatly in the literature. Mastoidectomy is thought to remove perisinus infection and granulation tissue, thereby reducing the thrombophilic nidus. Whether needle aspiration to confirm diagnosis or rule out a purulent thrombophlebitis is necessary and if subsequent thrombectomy alters disease progression is contested. In the same 20year review, Au et al. found that 54.9% of patients underwent needle aspiration and 47.1% thrombectomy, but the outcomes in these patients could not demonstrate superior efficacy of either treatment [10]. None of our patients underwent thrombectomy, but as mentioned above, one patient underwent IJ ligation for presumed septic pulmonary emboli. A significant benefit on the added utility of anticoagulant therapy has also yet to be definitely demonstrated in the current literature. Neilan et al. pooled data from eight studies for type of treatment and recanalization by follow-up imaging. Their group found that 20 out of 30 (66.7%) patients who were anticoagulated showed evidence of recanalization compared to 9 out of 17 (52.9%) who were not anticoagulated (P = 0.53) [15]. Limiting their review to the last 20 years, Au et al. reported 16 out of 19 (84%) anticoagulated patients and three of four (75%) non-anticoagulated patients demonstrated at least partial recanalization. Thirty-two out of 41 (78.6%) patients showed at least partial recanalization overall [10]. These numbers do suggest a trend toward an added benefit of anticoagulation, but lack the statistical power to draw definitive conclusions. If anticoagulation does increase the likelihood of at least partial recanalization following treatment, the next question is how the presence of recanalization translates to clinical significance in terms of symptom resolution or avoidance of neurological sequelae. In the case series presented by Sitton et al., five out of seven patients were asymptomatic at the time of discharge, one with no change in radiographic appearance several months later. Another patient had resolution of symptoms several months before imaging confirmed resolution, and another with persistent symptoms despite resolution on imaging 1 month after original diagnosis [7]. The difficulty in attributing significance to the use of anticoagulation in preventing neurologic sequelae is reinforced in our own experience. Two of our patients developed persistent symptoms. The first (Patient 1) was not treated with anticoagulation, while the second (Patient 3) did was treated with a 3 month course of anticoagulation. However, our first patient was the only patient with an initial diagnosis of meningitis, and his hospital course was complicated by intractable seizures, with clinical sequelae of epilepsy and developmental delay. The other patient developed a brain abscess and required multiple
Please cite this article in press as: J.L. Funamura, et al., Otogenic lateral sinus thrombosis: Case series and controversies, Int. J. Pediatr. Otorhinolaryngol. (2014), http://dx.doi.org/10.1016/j.ijporl.2014.03.002
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craniotomy procedures, each of which are independent risk factors for headache. We therefore have both examples of neurologic sequelae in both patients treated with and without anticoagulation with significant confounding factors within our own limited study. Another factor that may temper enthusiasm for routine use of anticoagulants in the management of lateral sinus thrombosis is the prospect of anticoagulation-related complications. Shah et al. reported two cases of post-operative hemorrhage related to low molecular weight heparin (enoxaparin, 1 mg/kg subcutaneously for every 12 h) [13]. Ropposch et al., on the other hand, presented a case series in which six patients were treated with low molecular weight heparin (enoxaparin, 1 mg/kg subcutaneously once a day) for 3 months after initial unfractionated heparin administration for 3 days post-operatively. Intermittent activated partial thromboplastin (aPTT) time and anti-factor Xa plasma levels were monitored, and no anticoagulant-related complications were evident. All patients had evidence of recanalization at 3 months, and the authors concluded that low molecular weight heparin is a safe treatment option when administered correctly [11]. In our series, we had an anticoagulant-related intracranial hemorrhage that did not require surgical intervention but resulted in early discontinuation of low molecular weight heparin (enoxaparin, 1.6 mg/kg subcutaneously every 12 h with normal anti-factor Xa levels). Low molecular weight heparin (enoxaparin) that is now a favored agent for long-term anticoagulation due to more predictable inhibition of coagulation enzymes resulting in the ability to administer fixed weight-adjusted doses without laboratory monitoring [11]. Enoxaparin is FDA-approved for treatment of thromboembolism at doses of 1 mg/kg subcutaneously every 12 h in patients greater than 2 months of age, and at 1.5 mg/kg in patients under 2 months of age. Efficacy and safety of enoxaparin in neonates and children has not been well-studied and therefore titration to effect of anti-factor Xa level of 0.5–1.0 U/mL 4–6 h postinjection is recommended [11,16]. Anticoagulation safety and efficacy have not been extensively studied in pediatric populations. Literature from other pediatric neurology and hematology literature was examined for prospective studies addressing this issue. In a recent and rare prospective study with a relatively large number of subjects, Moharir et al. followed pediatric patients with cerebral sinus thrombosis from all causes to measure bleeding complication and thrombus propagation with anticoagulation. Patients underwent pre- and postanticoagulation neuroimaging and monitored for major hemorrhagic events (hemoglobin drop >2 g/dL or requiring blood transfusion). Six percent (6/99) of anticoagulated patients had a major hemorrhagic event; all non-fatal and associated with comparable clinical outcomes as those without hemorrhage event. However, thrombus propagation was noted in 7/19 (38%) of children treated without, versus 3/44 (7%) treated with anticoagulation (p = 0.006), with worse clinical outcomes. These results led authors to state that anticoagulation appears safe in children with cerebral sinus thrombosis and merit strong consideration in treatment to improve clinical outcomes [16]. The state of current evidence suggests that the routine use of anticoagulation is not definitively supported based on a paucity of strong evidence for an independent or additive role in the treatment of lateral sinus thrombosis [10,15]. Anticoagulant therapy, however, has been shown to be generally safe in young
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children with proper monitoring [11,16]. Because rare anticoagulant-related complications will occur despite appropriate dosing and monitoring, the clinician must weigh this risk with the potential benefit of preventing thrombus propagation and improved clinical outcome [12,13,16]. Additional data will need to be collected in order to further guide clinicians in making this choice. Given the rarity of the condition and its potential for morbidity or mortality, we are currently reliant upon data collected via case series of experiences from individual institutions. Ongoing reports of medical and surgical therapy as well as outcome should therefore be encouraged to build an evidencebased management strategy of this rare intracranial complication of otitis media.
5. Conclusion The extent of surgery and the role of anticoagulation in the treatment of otogenic lateral sinus thrombosis are two major controversies that have yet to be resolved. Further data will be necessary in order to provide adequate evidence-based guidelines for the routine management of lateral sinus thrombosis.
References [1] C.D. Bluestone, J.O. Klein, Intracranial complications of otitis media and mastoiditis, in: C.D. Bluestone, et al. (Eds.), Pediatric Otolaryngology, 4th ed., Saunders, Philadelphia, 2003, pp. 772–774. [2] I. Bielecki, M. Cofala, J. Mierzwinski, Otogenic lateral sinus thrombosis in children, Otol. Neurotol. 32 (2011) 1111–1115. [3] C.B. Bales, S. Sobol, R. Wetmore, L.M. Elden, Lateral sinus thrombosis as a complication of otitis media: 10-year experience at the children’s hospital of Philadelphia, Pediatrics 123 (2009) 7009–7013. [4] N. Christensen, J. Wayman, J. Spencer, Lateral sinus thrombosis: a review of seven cases and proposal of a management algorithm, Int. J. Pediatr. Otorhinolaryngol. 73 (2009) 581–584. [5] K.E. Kelly, R.K. Jackler, W.P. Dillon, Diagnosis of septic sigmoid sinus thrombosis with magnetic resonance imaging, Otolaryngol. Head Neck Surg. 105 (1991) 617–624. [6] C. Virapongse, C. Cazenave, R. Quisling, M. Sarwar, S. Hunter, The empty delta sign: frequency and significance in 76 cases of dural sinus thrombosis, Radiology 162 (1987) 779–785. [7] M.S. Sitton, R. Chun, Pediatric otogenic lateral sinus thrombosis: role of anticoagulation and surgery, Int. J. Pediatr. Otorhinolaryngol. 76 (2012) 428–432. [8] G.E. Shambaugh, Jr., M.E. Glasscock (Eds.), Surgery of the Ear, Saunders, Philadelphia, 1980, pp. 302–309. [9] D.M. Kaplan, M. Kraus, M. Puterman, A. Niv, A. Leiberman, D.M. Fliss, Otogenic lateral sinus thrombosis in children, Int. J. Pediatr. Otorhinolaryngol. 49 (1999) 177–183. [10] J.K. Au, S.I. Adam, E.M. Michaelides, Contemporary management of pediatric lateral sinus thrombosis: a twenty year review, Am. J. Otolaryngol. 34 (2013) 145–150. [11] T. Ropposch, U. Nemetz, E.M. Braun, A. Lackner, C. Walch, Low molecular weight heparin therapy in pediatric otogenic sigmoid sinus thrombosis: a safe treatment option, Int. J. Pediatr. Otorhinolaryngol. 76 (2012) 1023–1026. [12] E. Novoa, M. Podvinec, R. Angst, N. Gurtler, Paediatric otogenic lateral sinus thrombosis: therapeutic management, outcome, and thrombophilic evaluation, Int. J. Pediatr. Otorhinolaryngol. 77 (2013) 996–1001. [13] U.K. Shah, T.F. Jubelirer, J.D. Fish, L.M. Elden, A caution regarding the use of lowmolecular weight heparin in pediatric otogenic lateral sinus thrombosis, Int. J. Pediatr. Otorhinolaryngol. 71 (2007) 347–351. [14] E.E. Tov, A. Leiberman, I. Shelef, D.M. Kaplan, Conservative nonsurgical treatment of a child with otogenic lateral sinus thrombosis, Am. J. Otolaryngol. 29 (2008) 138–141. [15] R.E. Neilan, B. Isaacson, J.W. Kutz Jr., K. Lee, P.S. Roland, Pediatric otogenic lateral sinus thrombosis recanalization, Int. J. Pediatr. Otorhinolaryngol. 75 (2011) 850– 853. [16] M.D. Moharir, M. Shroff, D. Stephens, A.M. Pontigon, A. Chan, D. MacGregor, et al., Anticoagulants in pediatric cerebral sinovenous thrombosis: a safety and outcome study, Ann. Neurol. 67 (2010) 590–599.
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