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11 Kavcic M, Fisher BT, Seif AE et al. Leveraging administrative data to monitor rituximab use in 2875 patients at 42 freestanding children’s hospitals across the United States. J. Pediatr. 2013; 162: 1252–8. 12 Curtillet C, Poullin P, Doré E et al. Paediatric case report of an acquired autoimmune thrombotic thrombocytopenic purpura. Arch. Pediatr. 2006; 13: 1521–4. 13 McDonald V, Liesner R, Grainger J et al. Acquired, noncongenital thrombotic thrombocytopenic purpura in children and adolescents: Clinical management and the use of ADAMTS 13 assays. Blood Coagul. Fibrinolysis 2010; 21: 245–50. 14 Harambat J, Lamireau D, Delmas Y et al. Successful treatment with rituximab for acute refractory thrombotic thrombocytopenic purpura related to acquired ADAMTS13 deficiency: A pediatric report and literature review. Pediatr. Crit Care Med. 2011; 12: e90–e93. 15 Narayanan P, Jayaraman A, Rustagi RS et al. Rituximab in a child with autoimmune thrombotic thrombocytopenic purpura refractory to plasma exchange. Int. J. Hematol. 2012; 96: 122–4.
16 Yagi H, Matsumoto M, Fujimura Y. Paradigm shift of childhood thrombotic thrombocytopenic purpura with severe ADAMTS13 deficiency. Presse Med. 2012; 41 (3 Pt 2): e137–55. 17 Westwood JP, Webster H, McGuckin S, McDonald V, Machin SJ, Scully M. Rituximab for thrombotic thrombocytopenic purpura: Benefit of early administration during acute episodes and use of prophylaxis to prevent relapse. J. Thromb. Haemost. 2013; 11: 481–90. 18 Tsai HM. Thrombotic thrombocytopenic purpura and the atypical hemolytic uremic syndrome: An update. Hematol. Oncol. Clin. North Am. 2013; 27: 565–84. 19 Jansson AF, Sengler C, Kuemmerle-Deschner J et al. B cell depletion for autoimmune diseases in paediatric patients. Clin. Rheumatol. 2011; 30: 87–97.
Rare but threatening complication of otitis media: Lateral sinus thrombosis I˙hsan Kafadar,1 Mukaddes Esra Sözen,2 Didem Büyüktas¸ Aytaç1 and Koray Yalçın3 Departments of 1Pediatrics and 2Ear Nose and Throat, S¸is¸li Etfal Training and Research Hospital and 3Department of Pediatrics, Okmeydanı Training and Research Hospital, Istanbul, Turkey Abstract
Although appropriate use of antibiotics has decreased mortality, lateral sinus thrombosis is a rare, important intracranial complication of acute otitis media. Herein is described the case of a 5-year-old patient with lateral sinus thrombosis after acute otitis media. We emphasize the need to be alert for lateral sinus thrombosis when treating acute otitis media.
Key words acute otitis media, intracranial complication, lateral sinus thrombosis.
The intracranial complications of otitis media include meningitis, venous sinus thrombosis, cranial nerve paralysis and intracranial abscess.1 In a child with middle-ear or mastoid infection, the presence of any systemic symptom, such as fever, headache, or lethargy, of extreme degree, or a finding of meningismus or of any central nervous system sign on physical examination should prompt suspicion of an intracranial complication. In lateral sinus thrombosis (LST), initially, a peri-sinus abscess is formed, and, as the infection penetrates the dura and approaches the intima, a mural thrombus develops. Damage to the intima of blood vessels, hypercoagulation, and decreased blood flow are contributory factors in the formation of thrombus within the vessels. The thrombogenic properties of bacteria are thought to accelerate the process. Unless effective treatment is Correspondence: Koray Yalçın, MD, Akdeniz University, Faculty of Medicine, Pediatric Hematology and Oncology, Antalya 07058, Turkey. Email: [email protected]
Received 17 February 2012; revised 13 May 2012; accepted 26 March 2014. doi: 10.1111/ped.12400
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properly instituted, the mural clot grows and necrotizes, forming an intramural abscess. Although the use of appropriate antibiotics has reduced mortality rates associated with LST from 100% to 5–35%, it still remains as a life-threatening complication.2,3 Antibiotic use may mask the symptoms and make diagnosis of LST more difficult.3,4 The masking of clinical symptoms and the overreliance on modern antibiotics may lead to the practical complications that may arise in the treatment of otitis media. In this case report we emphasize the need for medical doctors to be alert for LST during this treatment.
Case report A 5-year-old male patient presented with complaints of headache, fever, vomiting and loss of appetite. There was no considerable illness in the family history. Twelve days prior to presentation, the patient had visited a health center with similar complaints, underwent otoscopy that indicated hyperemia of the right tympanic membrane, and was treated with amoxicillinclavulinic acid (80 mg/kg per day for 14 days) for the presumptive diagnosis of right acute otitis media. He had no otalgia or
Lateral sinus thrombosis
Fig. 1 (a) Cranial magnetic resonance (MR) venography showing a filling defect in the lateral sinus; (b) Cranial MR showing hyperintensity in the lateral sinus.
otorrhea. Upon persistence of the complaints, the patient presented to the Ear, Nose and Throat Department, Sisli Etfal Training and Research Hospital, Istanbul. His general condition was normal and no peculiarities were noted on complete examination, including the neurological system. He was alert, conscious and responsive but lethargic. He had normal full blood count, blood biochemistry and coagulation parameters, and no family history of disease. Due to the persistence of the symptoms and the presence of headaches, cerebral computed tomography (CT) and magnetic resonance imaging (MRI) with cerebral magnetic resonance venogram were done (Fig. 1a). There was evidence of thrombosis in the right transverse and sigmoid sinus, diffuse thickening and intense contrast enhancement possibly secondary to inflammation in the dura, and right otomastoiditis (Fig. 1b). The patient was hospitalized and i.v. ceftriaxone (100 mg/kg per day for 14 days) and clindamycin (20 mg/kg per day for 14 days) were initiated. The homocysteine, protein C and S activity and anti-thrombin 3 antigen levels checked for the differential diagnosis of thrombosis were normal; anti-phosphatidylserine antibody, factor 5 Leiden mutation and prothrombin gene 20210 A mutation were negative. On the 10th day of hospital stay the patient developed diplopia for which a 7 day prednisolone treatment (2 mg/kg per day) was initiated. Follow-up cerebral MR angiography that was done on day 14 of hospitalization showed partial recanalization in the right transverse sinus, upon which 2 mg/kg per day acetylsalicylic acid treatment was initiated. Diplopia gradually disappeared on follow up, neurological examination was normal, otoscopy was normal and the control cranial MR venogram showed partial recanalization in the sinuses. The patient was discharged with recommendations of follow-up visits. At 3 month follow-up after discharge, the patient, who was still on 2 mg/kg per day acetylsalicylic acid, had normal neurological examination and cranial venogram, and no complaints were reported. Treatment duration was 6 months and future follow-up visits were scheduled. He had no problem at the 6 month posttreatment visit. His general condition was good and all systems were normal.
Discussion Lateral sinus thrombosis is a rare but threatening complication of otitis media and the resulting mastoiditis.5 LST occurs due to the direct dissemination of infection from the mastoid or the thrombophlebitis of the lateral sinus-related small veins of the mastoid.2 In a 2001 study, De Veber et al. reported the incidence of sinovenous thrombosis as 0.67 in 100.000 children per year.6 The use of strong and appropriate antibiotics and radiological imaging have now reduced the incidence of LST, but it still has a high mortality rate.2,7 In a study conducted in 1995, mortality rates due to sinus venous thrombosis (SVT) among children was found to be 16%, while the rate of long term sequelae was found to be 22%.8 Syms et al. reported an LST-related morbidity rate of 30%. These include septic cardiomyopathy, acute respiratory distress syndrome, anacousia, convulsion, ventriculoperitoneal shunt, and weakness in the upper extremity.9 Lateral sinus thrombosis is more prevalent among adults as a complication of chronic otitis media.2–4 Hereditary thrombotic conditions (anti-thrombin 3, protein C and S deficiency, factor 5 Leiden mutation, prothrombin gene 20210 A mutation) and acquired thrombosis (malignancy, autoimmune disease, myeloproliferative disease, antiphospholipid syndrome, pregnancy, oral contraceptive use) are risk factors in LST.10 In the present patient, LST had developed secondary to acute otitis media. The patient had no hereditary or previous disease, and LST risk factor examinations showed no pathologies. The most frequent presenting symptom is headache.5 If middle ear pathologies are accompanied by earache, vomiting, nausea, temperature, photophobia, neck stiffness, sixth and seventh nerve paralysis, lethargy and impaired consciousness, LST should be investigated.2–5,7 In the present patient, the general lethargy, recurring vomiting despite therapy and persisting headaches led to the preliminary diagnosis of LST. Most patients had increased number of leukocytes.3–5 When the current patient presented to our clinic, the number of leukocytes was within the limit for his age group. We attributed this to the 12 day © 2014 Japan Pediatric Society
I˙ Kafadar et al.
antibiotherapy that the patient received prior to presentation to our clinic. In LST diagnosis, cranial computed tomography (CT) shows mastoiditis, thickness in the dura around the sinuses, and filling defect in the lateral sinus, that is, the classic delta sign.2–5,7 The accompanying mastoiditis differentiates otogenic LST from secondary non-septic LST.5 In the present patient, the otomastoiditis detected on cranial imaging, together with other examinations for LST etiology, excluded secondary LST. In LST diagnosis, areas of hyperintensity are seen on MRI T1 and T2 sequences due to thrombosis,2–5 and MR venograph imaging shows signal loss and absence of sinus flow. MR venograms are more sensitive in the diagnosis of LST but they are at the same time more costly, and not all centers have the necessary equipment.3 In the present case, thrombosis was detected in the right transverse and sigmoid sinus on initial MR venogram. Digital subtraction angiograms, retrograde jugulograms and carotid arteriograms are also highly selective for LST but are invasive.2 Lateral sinus thrombosis is a rare condition and its treatment is debated.7 The literature reports the use of wide spectrum antibiotherapy and surgery as management options.3,4 The microbiology involved in the pathogenesis of LST is various. Proteus, Pseudomonas aeruginosa, Bacteriodes fragilis and anaeroba are most commonly found. In some cases, the middle ear culture remains negative.3 In the present patient, no agent pathogen was seen on middle ear culture. The necessary duration for antibiotherapy in the treatment of LST is not definite.7 In the present case we preferred ceftriaxone and clindamycin for 14 days. It is also stated that surgical treatment may be effective, and that the thrombus could be removed by mastoidectomy, lateral sinus vein exploration and sinus puncture.2 There is controversy about the use of anticoagulants and internal jugular vein (IJV) ligation in LST treatment. Anticoagulant use is not a standard treatment. It may lead to the dissemination of septic embolism or bleeding in the mastoid cavity.4 Thus, it is recommended for patients who have a high theoretical risk of infarction and embolization, and persistent septic thromboses.5 It is stated that anticoagulants should be considered if there are neurological changes, embolic situations, or persistent fever following an operation.5 Due to diplopia and persistent fever in the present patient and considering the duration from the beginning of the
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clinical episode, acetylsalicylic acid was initiated. Although the infection may be isolated and embolism may be prevented in the recommended LST treatment of IJV ligation, additional surgery complications may occur due to retrograde intracranial septic complications and cervical dissection. Some authorities have suggested IVJ ligation in cases of persistent post-mastoidectomy septicemia and septic pulmonary embolism.4 Conclusion
Even though LST, which is an intracranial complication of otitis media, occurs rarely, it is still a life-threatening condition. The important point is to consider intracranial complication when patients with otitis media have headaches, fever and impaired consciousness, requiring appropriate diagnostic methods and prompt treatment.
References 1 Munz M, Farmer JP, Auger L, O’Gorman AM, Schloss MD. Otitis media and CNS complication. J. Otolaryngol. 1992; 21: 224–6. 2 Ünsal EE, Ensari S, Koç C. A rare and serious complication of chronic otitis media: Lateral sinus thrombosis. Auris Nasus Larynx 2003; 30: 279–82. 3 Seven H, Ozbal AE, Turgut S. Management of otogenic lateral sinus thrombosis. Am. J. Otolaryngol. 2004; 25: 329–33. 4 Kaplan DM, Kraus M, Puterman M, Niv A, Leiberman A, Fliss DM. Otogenic lateral sinus thrombosis. Int. J. Pediatr. Otorhinolaryngol. 1999; 49: 177–83. 5 Bales CB, Sobol S, Wetmore R, Elden LM. Lateral sinus thrombosis as a complication of otitis media: 10-year experience at the Children’s Hospital of Philadelphia. Pediatrics 2009; 123: 709–13. 6 De Veber G, Andrew M, Adams C et al. Canadian Pediatric Ischemic Stroke Study Group. Cerebral sinovenous thrombosis in children. N. Engl. J. Med. 2001; 345: 417–23. 7 Christensen N, Wayman J, Spencer J. Lateral sinus thrombosis: A review of seven cases and proposal of a management algorithm. Int. J. Pediatr. Otorhinolaryngol. 2009; 73: 581–4. 8 De Veber G, Andrew M, Adams M et al. Treatment of pediatric sinovenous thrombosis with low molecular weight heparin (Abstract). Ann. Neurol. 1995; 38: 32. 9 Syms MJ, Tsai PD, Holten MR. Management of lateral sinus thrombosis. Laryngoscope 1999; 109: 1616–20. 10 Bianchini C, Aimoni C, Ceruti S, Grasso DL, Martini A. Lateral sinus thrombosis as a complication of acute mastoiditis. Acta Otorhinolaryngol. Ital. 2008; 28: 30–33.