Gradenigo syndrome is rare, but has serious potential complications.
Case Description
A nine-year old boy presents to the emergency department complaining of headache, left sided facial pain, blurry vision, diplopia and vomiting. Previously, he had been seen on two other occasions by his primary doctor for drainage from the left ear and had been prescribed Cefdinir and Oflaxacin otic drops. He denies fever, cough or rhinorrhea and is an otherwise healthy child. Surgical history is notable for tonsillectomy, adenoidectomy and bilateral myringotomy tubes. His allergies include Amoxicillin, Biaxin and Ibuprofen. His vaccines are up to date. Family history is non-contributory.
Physical exam shows a well-appearing boy in no acute distress. His temperature is 97.4, blood pressure 106/75, heart rate 76, and respiratory rate 22. There is mild lateral gaze palsy and esotropia that is greater on the left. The remainder of the cranial nerves are intact. There is no papilledema. The right tympanic membrane demonstrates chronic changes and the left tympanic membrane cannot be visualized due to purulent drainage. There is no mastoid bone tenderness to palpation or erythema. The patient has no sinus tenderness to palpation and there is no oropharyngeal erythema or exudate. His neck is supple and there is no meningismus. Remainder of the neurologic exam is normal. The patient’s heart is regular rate and rhythm without murmur. His lungs are clear to auscultation bilaterally and his abdomen is soft and nontender. There are no rashes or lesions visible on exam of the skin.
The patient is given an oral analgesic for pain control. Labs including a CBC and BMP are ordered and a CT scan of the head is obtained. The patient’s WBC count is slightly elevated at 11.1. Otherwise, the labs are normal. The CT head is negative for intracranial hemorrhage, mass, or midline shift. The ventricles and sulci are within normal limits. There is bilateral mastoid air cell opacification and inflammatory changes of the petrous bone on the left. After reviewing the CT images, the radiologist contacts the emergency medicine physician and recommends that an MRI of the brain with and without contrast be obtained to aid with further evaluation. The patient’s MRI brain demonstrated apical petrositis, dural venous sinus thrombosis of the left sigmoid sinus with caudal extension into the jugular vein, and possible involvement of a portion of the transverse sinus.
He was admitted to the Pediatric Intensive Care Unit. Neurosurgery was consulted and recommended MRA, MRV and a lumbar puncture. He was treated with Ceftriaxone and Vancomycin pending CSF culture results. Due to concern for increased intracranial pressure secondary to venous sinus thrombosis he was started on Dexamethasone, Diamox and Lovenox. A hypercoagulability work up was negative. He had bilateral myringotomy tubes placed by Otolaryngology and was continued on Ofloxacin otic drops. CSF cultures were negative and bilateral ear cultures grew Group A Strep.
The patient was discharged home on Cefuroxime and Lovenox. At time of discharge his headache and emesis had resolved, but he only had mild improvement of his diplopia and no change of his left esotropia.
He returned to the Emergency Department nine days later with complaints of worsening persistent headache and vomiting. He had papilledema on fundoscopic exam. He was admitted to the Neurosurgical service where a repeat MRI / MRV revealed no acute abnormality, patency of the venous sinuses and internal jugular vein. A lumbar puncture revealed extremely high opening pressures that required placement of a lumboperitoneal shunt.
The patient was discharged home on Cefdinir and Lovenox. At the time of discharge he had complete resolution of his headache, emesis, diplopia and abducens nerve palsy.
Discussion
Acute otitis media is a condition commonly treated in the Pediatric Emergency Department. Complications arising from acute otitis media have become much less common in the era of widespread antibiotic use. (1,3,4) Gradenigo syndrome and dural venous sinus thrombosis are rare, but have serious potential complications. The death rate of lateral and sigmoid sinus thrombosis has been reported to be in the range of 5-35%. (7)
To our knowledge, after performing an extensive literature search, there are no reported cases of suppurative acute otitis media complicated by Gradenigo syndrome and dural venous sinus thrombosis with subsequent benign intracranial hypertension requiring placement of a lumboperitoneal shunt.
The diagnosis of Gradenigo syndrome was made on the basis of the patient’s history and clinical exam findings of suppurative acute otitis media, facial pain in the trigeminal nerve distribution, and diplopia from an ipsilateral abducen’s nerve palsy. (1,3,9,12) His CT demonstrated petrous apicitis consistent with Gradenigo syndrome. Additionally, MRI/MRV revealed a dural venous sinus thrombosis of the left sigmoid sinus with caudal extension into the jugular vein.
Time intervals between the onset of acute otitis media and the manifestation of cranial nerve dysfunction vary between a week and two- to three-months. (1,8) Clinical presentation can be initially subtle and difficult to diagnose. The neurological manifestations of Gradenigo Syndrome are attributed to the proximity of cranial nerves to the petrous apex. (4,8,9,10) The trigeminal nerve ganglion and abducens nerve are the two most common cranial nerve deficits. They are the most susceptible to an adjacent inflammatory reaction as they are only separated from the petrous apex by a thin layer of dura matter. (10,12) Facial sensory dysfunction and retrobulbar pain is secondary to irritation of the trigeminal nerve. Lateral rectus palsy and subsequent diplopia result from inflammation involving the abducens nerve. (10)
Dural venous sinus thrombosis can be septic or aseptic in origin. A septic origin is due to an infection causing thrombophlebitis whereas an aseptic etiology is secondary to hypercoagulable conditions, trauma, or iatrogenic causes. (7) Middle ear infections cause venous sinus thrombosis by direct spread or via the emissary veins. (7) The most common presenting symptoms are headache, otalgia and fever. (4,8) Thrombosis of the dural venous sinuses can lead to increased intracranial pressure due to the obstruction of venous outflow with subsequent venous engorgement and potentially impaired cerebrospinal fluid absorption. Patients may therefore present with severe headache, vomiting, ocular palsies, visual changes, papilledema and lethargy.
CT scan is the imaging of choice to evaluate for petrous apicitis due to its sensitivity and low false positive rate. (3,9,10,12) MRI and MR Venography is the preferred imaging for suspected thrombophlebitis as CT scan has up to a 40% false negative rate for lateral sinus thrombosis. (5,8)
Treatment
Treatment of Gradenigo syndrome is typically with intravenous antibiotics. (9,12) Otolaryngology should be consulted early as surgical intervention is warranted if patients fail medical therapy, have cranial nerve palsies or develop an abscess. (9) Initial surgical management is often insertion of tympanostomy tubes. (2) More recent studies have demonstrated the safety and efficacy of conservative otological surgery and anticoagulant therapy for treatment of sinus venous thrombosis. (5,6,8,11)
As reported in prior studies, medical therapy with antibiotics and anticoagulants has achieved complete resolution of symptoms of Gradenigo Syndrome with associated sinus venous thrombosis. (8) Our patient returned to the Children’s Emergency Department after nine days with signs and symptoms suggestive of worsening increased intracranial pressure. The elevated opening pressures on lumbar puncture, but normal MRI/MRV findings were surprising and suggestive of benign intracranial hypertension.
In conclusion, otological complaints are common in the Pediatric Emergency Department.
These rare, but potentially fatal complications must be considered in our differential diagnosis. A high index of suspicion can lead to early recognition and treatment.
References
- Taklalsingh N, Falcone F, Velayudhan V. Gradenigo’s Syndrome in a Patient with Chronic Suppurative Otitis Media, Petrous Apicitis, and Meningitis. Am J Case Rep. 2017 Sep 28;18:1039-1043. PubMed PMID: 28955030; PubMed Central PMCID: PMC5629926.
- Vitale M, Amrit M, Arora R, Lata J. Gradenigo’s syndrome: A common infection with uncommon consequences. Am J Emerg Med. 2017 Sep;35(9):1388.e1-1388.e2. doi: 10.1016/j.ajem.2017.07.020. Epub 2017 Jul 5. PubMed PMID: 28720403.
- Jensen PV, Hansen MS, Møller MN, Saunte JP. The Forgotten Syndrome? Four Cases of Gradenigo’s Syndrome and a Review of the Literature. Strabismus. 2016;24(1):21-7. doi: 10.3109/09273972.2015.1130067. Epub 2016 Mar 16. Review. PubMed PMID: 26979620.
- Janjua N, Bajalan M, Potter S, Whitney A, Sipaul F. Multidisciplinary care of a paediatric patient with Gradenigo’s syndrome. BMJ Case Rep. 2016 Feb 25;2016. pii: bcr2015214337. doi: 10.1136/bcr-2015-214337. PubMed PMID: 26917799; PubMed Central PMCID: PMC4769448.
- Zanoletti E, Cazzador D, Faccioli C, Sari M, Bovo R, Martini A. Intracranial venous sinus thrombosis as a complication of otitis media in children: Critical review of diagnosis and management. Int J Pediatr Otorhinolaryngol. 2015 Dec;79(12):2398-403. doi: 10.1016/j.ijporl.2015.10.059. Epub 2015 Nov 5. PubMed PMID: 26590005.
- Wong BY, Hickman S, Richards M, Jassar P, Wilson T. Management of paediatric otogenic cerebral venous sinus thrombosis: a systematic review. Clin Otolaryngol. 2015 Dec;40(6):704-14. doi: 10.1111/coa.12504. Review. PubMed PMID: 26769686.
- Balasubramanian A, Mohamad I, Sidek D. Extensive dural sinus thrombosis and bilateral lateral rectus palsy as an uncommon complication of chronic suppurative otitis media. BMJ Case Rep. 2013 Jan 25;2013. pii: bcr2012007414. doi: 10.1136/bcr-2012-007414. PubMed PMID: 23355565; PubMed Central PMCID: PMC3603784.
- Scardapane A, Del Torto M, Nozzi M, Elio C, Breda L, Chiarelli F. Gradenigo’s syndrome with lateral venous sinus thrombosis: successful conservative treatment. Eur J Pediatr. 2010 Apr;169(4):437-40. doi: 10.1007/s00431-009-1047-4. Epub 2009 Aug 21. PubMed PMID: 19697060.
- Burston BJ, Pretorius PM, Ramsden JD. Gradenigo’s syndrome: successful conservative treatment in adult and paediatric patients. J Laryngol Otol. 2005 Apr;119(4):325-9. PubMed PMID: 15949093.
- Sherman SC, Buchanan A. Gradenigo syndrome: a case report and review of a rare complication of otitis media. J Emerg Med. 2004 Oct;27(3):253-6. PubMed PMID: 15388211.
- Stam J, De Bruijn SF, DeVeber G. Anticoagulation for cerebral sinus thrombosis. Cochrane Database Syst Rev. 2002;(4):CD002005. Review. Update in: Cochrane Database Syst Rev. 2011;(8):CD002005. PubMed PMID: 12519565.
- Motamed M, Kalan A. Gradenigo’s syndrome. Postgrad Med J. 2000 Sep;76(899):559-60. Review. PubMed PMID: 10964120; PubMed Central PMCID: PMC1741722
1 Comment
I read this case report with a lot of interest as my son, at age 10, had much the same. He had a URI that progressed to right ear fullness, headache, and lethargy, and on exam had a clear right otitis media. He began antibiotics and that evening his TM perforated but rather than begin to feel better, the next afternoon he questioned why I had “two heads”. His cranial nerve exam was normal at that time, but by the next day he had developed a dense right 6th CN palsy, and though his MRI was read as normal, the MRV showed a complete occlusion of his right sigmoid sinus which eventually extended into the jugular vein as well as right-sided mastoiditis. He also had papilledema on exam.
He underwent emergent mastoidectomy, and in the OR had his first LP, which showed elevated ICP of nearly 50cm H2O, and they drained off 35cc of CSF. Post-operatively he was begun on heparin and transitioned to enoxaparin and eventually warfarin.
Despite resolution of his cerebral venous thrombosis, his 6th CN palsy persisted for some weeks, and though one neurologist recommended a shunt (as was done in this case), another opined that his arachnoid villi might be obstructed (as a consequence of his CVT), and hoped they would open up in time. My son underwent a total of 4 LPs, each demonstrating high ICP, and each time a large volume of CSF was drained, but gradually his lateral nerve palsy resolved.
He remained on anticoagulation for months and had a prolonged course of parenteral antibiotics as well. A hypercoaguable workup was negative. He’s now 21, just graduated college, and has never had anything like this again.
Take home points:
1. Look for papiledema in patients like this with any hint of CN palsy. Most CVT patients develop this.
2. If you suspect CVT, MRV (or perhaps CTV) is the study of choice.
3. Lateral nerve palsy may simply be due to elevated ICP, and not direct nerve inflammation, as proposed in this case.
4. Give it time and repeated LPs if needed. Rather than invoke a second dx of benign intracranial hypertension, it’s more likely obstruction of CSF drainage, which (at least in my son) resolved over time.