International Journal of Pediatric Otorhinolaryngology Extra 6 (2011) 100–103

Case report

Successful prolonged conservative treatment of Gradenigo’s syndrome ina 4-year-old girl: A case report and literature review

Elodie Marteau a, Emilie Georget-Bouquinet a, Suzanne Verlhac b, Anne Gauthier c,Natacha Remus a, Fouad Madhi a,*a Service de Pediatrie, Centre Hospitalier Intercommunal de Creteil, 40 avenue de Verdun, 94000 Creteil, Franceb Service de Radiologie, Centre Hospitalier Intercommunal de Creteil, 40 avenue de Verdun, 94000 Creteil, Francec Service d’ORL, Centre Hospitalier Intercommunal de Creteil, 40 avenue de Verdun, 94000 Creteil, France

A R T I C L E I N F O

Article history:

Received 15 March 2010

Received in revised form 26 April 2010

Accepted 27 April 2010

Available online 23 May 2010

Keywords:

Gradenigo’s syndrome

Acute otitis media

Sixth nerve palsy

Mastoiditis

Petrositis

A B S T R A C T

Gradenigo’s syndrome, one of the complications of middle ear infection, is characterised by

persistent otorrhoea, pain in the region innervated by the first and second divisions of the trigeminal

nerve and ipsilateral abducens nerve palsy. We report the case of a 4-year-old girl with Gradenigo’s

syndrome. Computed tomography and magnetic resonance imaging provided evidence of infection

of the apex of the petrous temporal bone. The patient received an appropriate antibiotic therapy but

the recurrence of symptoms responded to the prolongation of a conservative treatment without

surgical intervention.

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1. Introduction

The Gradenigo’s syndrome (GS), described by GiuseppeGradenigo in 1907 (also called Gradenigo–Lannois syndrome orpetrous apicitis) [1], consists of a triad of purulent otorrhoea, facialneuralgia and paralysis of the sixth cranial nerve. Since theemergence of antibiotics in the systematic treatment of acute otitismedia (AOM), this previously well-known complication, hasbecome rare, explaining the difficulties of diagnosis and manage-ment today. The diagnosis is based on clinical signs and brainimaging, showing petrositis (osteitis of the apex of the petroustemporal bone due to diffusion of infection of the middle ear viamastoid cells towards its tip). We describe the case of a 4-year-oldgirl with GS and then we discuss the present management of thissyndrome, in particular the indication of anti-microbial therapy.

2. Case

A 4-year-old girl presented with a two-week history of right-sided otorrhea. She received a 6-day course of oral amoxicilline andclavulanic acid and oral prednisolone at a dose of 1 mg/kg/d. Theappearance of periorbital facial neuralgia at day 10 and, 2 days

* Corresponding author. Tel.: +33 1 45 17 53 98; fax: +33 1 45 17 54 26.

E-mail address: Fouad.Madhi@chicreteil.fr (F. Madhi).

1871-4048/$ – see front matter � 2010 Elsevier Ireland Ltd. All rights reserved.

doi:10.1016/j.pedex.2010.04.005

later, of paralysis of the sixth cranial nerve suggested the diagnosisof GS. Our patient was afebrile but suffered from headache andvomiting. The leucocyte count was 17 900/mm3 with a predomi-nance of polymorphnuclear neutrophils (14 200/mm3) and 2770lymphocytes/mm3 lymphocytes. The C-reactive protein was50.7 mg/l. Bacterial cultures of the auricular secretions, bloodand cerebro-spinal fluid were negative.

The diagnosis of the GS was confirmed by computed tomogra-phy (CT) and magnetic resonance imaging (MRI) revealing right-sided mastoiditis, involvement of the apex of the petrous temporalbone (Fig. 1), widening and heterogeneity of the lodge of the rightcavernous sinus as well as enhancement of the surroundingmeninges.

The patient was treated with intravenous ceftriaxone (100 mg/kg/d) and fosfocine (150 mg/kg/d) for 7 days followed by oralamoxicilline and clavulanic acid during 7 days, associated tocorticosteroid with prednisolone (2 mg/kg/d) during 8 days. Shewas discharged from hospital on the 21th day of the disease whenfacial neuralgia had disappeared but sixth cranial nerve palsypersisted.

On the 32th day, our patient again presented with facialneuralgia of several-day duration and still persisting sixth nervepalsy. The clinical examination found a temperature of 38.1 8C, achange of the general health status (2 kg weight loss in 1 month)with signs of right-sided fifth (V) and sixth cranial nerve (VI)involvement (Fig. 2). There was neither meningeal irritation, nor

Fig. 1. MRI. Axial image T2 weighted. Hypersignal of the right mastoid and petrous

apex indicated by the arrows.

Fig. 3. CT scan. Axial view. Thrombosis of the right cavernous sinus (thickening with

a heterogenous aspect like a ‘‘comet-tail’’).

E. Marteau et al. / International Journal of Pediatric Otorhinolaryngology Extra 6 (2011) 100–103 101

alteration of consciousness. Both tympanic membranes werecongestive without otorrhea and the throat was erythematous.

The leucocyte count (9900/mm3) and the CRP (50.4 mg/l) wereonly slightly elevated as in the initial presentation and bacterial earswabs and blood cultures were again negative.

Fig. 2. Right abducens nerve palsy, (A) looking straight ahead; (B) looking to the left;

(C) looking to the right.

The cranial CT scan with contrast performed at admissionshowed right-sided mastoiditis, thrombosis of the right cavernoussinus (thickening with a heterogenous aspect like a ‘‘comet-tail’’)and contrast enhancement of the adjacent meninges withoutosteolytic lesions or intra-cerebral fluid collection (Fig. 3). The MRIdemonstrated a stenosis of the right carotid artery and theprecommunicating segment of the right anterior cerebral arterywith parietal thickening (Fig. 4).

A triple intravenous antibiotic therapy, including cefotaxime(300 mg/kg/d) and metronidazole (30 mg/kg/d) for 3 weeks andrifampicine (20 mg/kg/d) for 10 days, was followed by a 5-weekcourse of oral amoxicilline and clavulanic acid. A curativeanticoagulation with low molecular weight heparin (Innohep175 UI/kg/d) was introduced for a period of 3 months. The patientwas afebrile from the first day of intravenous antibiotic therapyand the CRP became normal after 1 week of treatment. Totalimmunoglobulin and immunoglobulin subclass levels, lymphocyte

Fig. 4. Three-dimensional time-of-flight (3D TOF) Magnetic resonance angiography

(MRA). Willis’s polygone. Right carotid and anterior cerebral artery stenoses.

E. Marteau et al. / International Journal of Pediatric Otorhinolaryngology Extra 6 (2011) 100–103102

phenotypes and neutrophil chemotactism (nitroblue tetrazoliumtest; NBT) were normal. A thrombophilia screen was negative. Theoutcome was favorable with disappearance of facial neuralgia andthere was a complete recovery of the sixth nerve palsy by the endof the intravenous therapy.

Imaging (CT and MRI) performed 3 months after the start of thesecond intravenous antibiotic therapy, confirmed the clinicalimprovement with improvement of the right cavernous sinusthrombosis and carotid arteritis.

3. Discussion

The GS consists of the association of otitis media, pain in theregions innervated by the first and second division of thetrigeminal nerve (fifth cranial nerve) and abducens nerve (sixthcranial nerve) palsy [1]. However, only about 42% of patientspresent the full triad of symptoms [2].

It is thought that the manifestations of the syndrome resultfrom the extension of an inflammatory process, that begins inthe middle ear and reaches the top of the petrous part of thetemporal bone. Cranial nerve dysfunction is caused by osteitisand local leptomeningitis near the apex of the petrous bone.There, the trigeminal nerve ganglion and the abducens nerve lieclosely together, separated from the apex of the petrous boneonly by the dura mater. Inflammation of the Gasser ganglioncontaining the Vth cranial nerve and of Dorello’s canal, which isthe orifice of the VIth nerve, explains involvement of the cranialnerves and the clinical symptoms. The delay of the extension ofthe inflammatory process determines the onset of symptomsand varies between 1 week and 3 months, according to theliterature [3–5].

The responsible organisms are rarely identified, but most of thetime Pseudomonas aeruginosa (PA) is found, followed by Strepto-

coccus groupe A, Staphylococcus aureus, anaerobic bacteria, rarelynon-hemolytic Streptococcus constellatus or acidominimus or evenMycobacterium tuberculosis [3,4]. Particular attention should bepaid to Fusobacterium necrophorum, an anaerobic organism, alsoimplicated in Lemierre’s syndrome. Regarding the PA, its involve-ment in the development of acute otitis externa or malignant otitisexterna (particularly in diabetic or human immunodeficiency virusinfected patients) has been clearly identified but its implication inAOM remains a matter of discussion [6]. Nevertheless, severalstudies isolated PA in 20–25% of children with AOM with temporalbone or intra-cerebral complications or with acute mastoiditis [7].Additionally, PA has been found in recurrent and chronic AOM withsimilar frequency [8].

Cerebral imaging studies with CT and MRI are the methods ofchoice for diagnosis. They not only allow assessing the extension ofthe lesions and identifying complications of the GS but also helpeliminate differential diagnoses and distinguish between acuteand chronic forms of petrositis [9–13]. The acute form usuallyaffects children while the chronic form is frequently observed inadults [14].

The management of this syndrome has not been codified yetdue to the small number of cases reported. Thus, all the authorsadvocate urgent care in view of the severity of GS and its potentialcomplications. A conservative treatment is preferred as the clinicaland radiological outcome is mostly favorable, avoiding surgicaltreatment [3]. A conservative treatment includes a wide-spectrumantibiotic therapy with two or three antibiotics that achievesufficient concentrations in the brain parenchyma. The antibioticsare initially given intravenously followed by an oral mono-therapy,that is often prolonged from 5 to 8 weeks [3,5,15,16].

Only few authors advocate broad-spectrum antibiotic therapycovering PA. In our case, the evolution has been favorable, althoughthe antibiotic regimen did not cover this organism.

There are no recommendation regarding duration of theantibiotic therapy, but a recent review of the literature observeda favorable outcome for most of the patients with variable length oftherapy [3,4,17]. The current tendency is to privilege an extendedperiod of intravenous followed by oral antibiotic therapy. Indeed,the recurrence of symptoms and complications (thrombosis of thecavernous sinus, carotid arteritis) in our case 1 month after initialpresentation, might be attributable to the short duration ofantibiotics (initially 2 weeks), rather than their respectivespectrum of action. This means that the recurrence of symptomsis not related to the failure of a conservative treatment.

A surgical treatment, consisting of a mastoidectomy and adrainage of the petrous apex, should be reserved to failures of aconservative treatment and to chronic forms which might suggestinsufficient concentrations of antibiotics in the brain parenchyma[3].

Sinus thrombosis and GS are rare but potential fatal complica-tions of AOM and mastoiditis, probably favored by the severity oflocal inflammatory mechanisms. This complication most frequent-ly affects the lateral or sigmoid sinuses [2,13,14,17]. Theintroduction of anticoagulation at a curative dose in the presenceof thrombosis of one or more sinuses is controversial. It has beendemonstrated that thrombosed sinuses do become permeablewith and without an anticoagulant treatment after similar timelapses [2,16,18]. In our case, the introduction of effective antic-oagulation was followed by a favorable radiological evolution fromthe first month of treatment (complete disappearance of the imageof the thrombus). Regarding the anticoagulant, the currentrecommendations in children advocate low molecular weightheparin (LMWH) for at least 3 months [14,19].

The corticosteroid treatment is also a topic of discussion. Someauthors recommend their use to reduce the risk of cerebral oedemaand signs of intra-cranial hypertension resulting from thrombosisof the sinuses of the base of the skull. It would also reduceinflammation of cranial nerves thus accelerating recovery[2,10,14,15]. However, these benefits have not been clearlydemonstrated. Our patient, treated for 14 days with prednisolone,recovered as rapidly as patients without such a treatment, but therole of corticosteroids in the recurrence of her symptoms is notclear. It is clear that this therapy cannot be used in cases of GS withmeningitis or uncontrolled infectious processes and thus we do notrecommend the use of corticosteroids as first-line treatment in thissyndrome.

Usually prognosis is favorable and no case of seriouscomplications or death have been reported since the second halfof the 20th century. Physicians should be aware of this raresyndrome. Early diagnosis and management are important toprevent complications and sequelae.

4. Conclusion

Although rare, life-threatening complications of AOM stilloccur, like in the case presented here. In the presence of anunilateral facial pain and a sixth nerve palsy, GS should beconsidered and treatment should be administered rapidly in orderto avoid complications. A conservative medical treatment withoutsurgery is usually successful.

References

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