yi-tsen, lin. introduction pathophysiology pathogens clinical manifestations laboratory studies...

Yi-Tsen, Lin

IntroductionPathophysiologyPathogensClinical manifestationsLaboratory studies ImagingMedical treatmentSurgical treatmentPrognosis

1959, Meltzer and Keleman: Bacillus pyocyaneus osteomyelitis of

temporal bone in a diabetic patient

1968, Chandler: Malignant otitis externa

Skull base osteomyelitis

Malignant otitis externa

Chronic otitis media

Osteoradionecrosis

Soft tissue infection of the ear canal Spread via the fissures of Santorini and the

tympanomastoid suture Via venous channels and fascial planes within

the temporal bone Along the middle and posterior fossa surfaces Reaching the petrous apex (Gradenigo’s

syndrome) May cross midline

The otic capsule exhibits significant resistance.

Spread to skull base and involvement of IX, X, XI cranial nerves (Vernet’s syndrome)

Intracranial invasion: Meningitis Intracranial abscess Septic thrombosis of the sigmoid sinus or

internal jugular vein

Extracranial extension: Prevertebral / parapharyngeal abscess Spread to sympathetic plexus around carotid

sheath

Bacteria Pseudomonas aeruginosa Staphylococcus epidermidis Staphylococcus aureus Klebsiella spp. Proteous spp. Non-tuberculous mycobacteria (NTM)

Fungus Aspergillus fumigatus

Pseudomonas aeruginosa Gram-negative, obligate aerobic bacillus Not normal flora of the ear canal Colonization after significant water

exposure or minor trauma A mucoid layer carrying lytic enzymes

necrotizing vasculitis

Non-tuberculous mycobacteria (NTM) Mycobacterial species other than the M.

tuverculosis complex or M. lerae

Rapidly growing mycobacteria Slowly growing mycobacteria

Diagnosis: ▪ Repeated isolation of the same NTM species ▪ Typical granulomas or presence of mycobacteria

on histopathology

Fungus Less commonly associated with diabetic

patients Immunocompromised patients (e.g. HIV,

hematologic malignancies) History of chronic otitis media

Most common: Aspergillus fumigatus

Diabetic patients Defects in: chemotaxis, phagocytosis,

oxidative burst and killing function of PMNs, and cellular immunity

Neutral pH of the cerumen Diabetic microangiopathy Ischemia

P. aeruginosa infections

Patients with HIV infections Decreased numbers of CD4 T cells Impaired chemotaxis and neutrophil

degranulation Blunted humoral immue response

P. aeruginosa infections (CD4 <100/mm3) Invasive Aspergillus infections (CD4

<50/mm3)

After water exposure or trauma “Deep” otalgia

Severe, unremitting, and throbbing pain May accompanying headache and TMJ pain Worse at night Refractory to analgesics

Fever is uncommon.

Diabetic or immunocompromised patients

A tender and swollen external auditory canal

A granulomatous polyp in the floor of the external auditory canal at the bony-cartilaginous junction

Cranial nerve palsy (Most common: CN7)

Petrous apicitis1907, Gradenigo:

Triad: Constant otorrhea, headache, diplopia

Diagnostic Criteria Suppurative otitis media Pain in the distribution of the trigeminal

nerve Abducens nerve palsy

Jugular foramen syndromeParalysis of the glossopharyngeal,

vagus, and accessory cranial nervesCauses:

Skull bass osteomyelitis Trauma VZV infection Cholesteatoma Giant cell arteritis

Culture

Tissue biopsy

Laboratory studies

Image studies

LeukocytosisErythrocyte sedimentation rate (ESR)

Evaluation for diabetes

HRCT of temporal bone

MRI

Technetium-99 SPECT

Gallium-67 Scan

Skull base bone destruction More than 30% of affected bone

demineralization to appear eroded on CT Abscess formation

Not an appropriate exam to evaluate response Remineralizaiton of afflicted bone may

never occur despite resolution of the infection.

Erosion of the tympanic plate along the posterior margin of the

mandibular fossa

Erosion of the tympanic plate along the posterior margin of the

mandibular fossa

Identifying soft tissue changesHigh signal intensities on T2-WIsDural enhancement Involvement of the medullary space

of bone

Change in MRI do not resolve with disease.

Trigeminal ganglion in Meckel cave

Trigeminal ganglion in Meckel cave

CN6 Abducens Nerve

CN6 Abducens Nerve

Jugular ForamenJugular Foramen

Hypoglossal canalHypoglossal canal

Petrous apex (small arrow)Constriction of the carotid artery (large arrow)

Petrous apex (small arrow)Constriction of the carotid artery (large arrow)

Invovement of infratemporal fossa

Invovement of infratemporal fossa

Invovement of paraspinal space

Invovement of paraspinal space

Areas of increased osteoblastic activity Infection, trauma, neoplasm, and

postoperative conditions

Three phase bone scan Immediately after injection (blood flow phase) 15 minutes after injection (blood pool phase) 4 hours after injection (osseous phase)

Osteomyelitis: intense uptake in all 3 phases

Earlier diagnosis of osteomyelitis Bone demineralization need not be

present.

The 99Tc bone scan remains positive for several months after clinical resolution. Bone repair continues for a prolonged

period after injury.

Grade I: Mild uptakeGrade II: Focal mastoid/temporal bone uptake not reaching midlineGrade III: Petrous temporal bone uptake reaching midlineGrade IV: Uptake crossing midline to involve the contralateral side

Grade I: Mild uptakeGrade II: Focal mastoid/temporal bone uptake not reaching midlineGrade III: Petrous temporal bone uptake reaching midlineGrade IV: Uptake crossing midline to involve the contralateral side

Areas of active inflammation (infection) by binding to acute phase reactants

It should be repeated every 4 weeks to monitor antibiotic response until it is normal.

It returns to normal sooner once the infection is resolved.

Antipseudomonal antibiotics Ceftazidime Ciprofloxacin

Ticarcillin or piperacillin 3rd or 4th cephalosporin (e.g. cefepime) Carbapenem (e.g. imipenem)

Ceftazidime A third generation cephalosporin Bactericidal activity against P.

aeruginosa Monotherapy Combined with an aminoglycoside to:

▪ Broaden the spectrum▪ Reduce resistance▪ Potentially improve treatment result

Ciprofloxacin Strong bone penetration Effectiveness against Pseudomonas Rapid accumulation in tissue with oral

administration A mild side effect profile Rising resistance? Magnesium salts reduces GI absorption. Concurrent administration with theophylline

can lead to toxicity.

Treatment time At least 4 to 8 weeks A change to oral antibiotic after an initial

2 week course of IV combined therapy in patients with early disease

The previous treatment of these patients with topical or oral antibiotics often leads to negative cultures of the external auditory canal.

Bacterial identification and sensitivities ?

Djalilian HR et al. 2006

A retrospective study 8 consecutive patients over a 2-year

period Median age: 54 years (42-84 yr) Comorbidity: all pts with DM Treatment

Topical polymyxin, neomycin, and hydrocortisone

Oral ciprofloxacin (750mg two times per day) Intravenous ceftazidime (2g every 12 hours)

▪ Peripheral intravenous central catheter (PICC)

NTM infection (combination therapy) Antibiotics

▪ Duration of medical treatment: average 7 months

▪ Until a disease free period of 4-6 months Surgical debulking or clearance of

disease

Petrini B 2008

BiopsyDebridement of granulation tissueDecompression of cranial nerves

The first-line treatment of osteomyelitis in areas other than the cranial base includes aggressive debridement of devitalized tissue.

MastoidectomyPetrosectomy

Infracochlear approach Transmastoid infralabyrinthine approach Middle fossa approach Translabyrinthine approach Transotic appoach

Infracochlear approach

Infracochlear approach

Transmastoid infralabyrinthine approachTransmastoid infralabyrinthine approach

Middle fossa approach

Middle fossa approach

Translabyrinthine approach

Translabyrinthine approach

Transotic approachTransotic approach

Removal of the bone circumferentially around the sound conduction/transduction pathway

Intraoperative facial and trigeminal nerve monitoring

Visosky AMB et al. 2006

A curved incision begins at 0.2 cm posterior and inferior to the mastoid tips, and ends at the zygomatic zoot in the preauricular crease.

The skin and temporoparietal fascia is reflected anteriorly and inferiorly.

The temproralis muscle is reflected inferiorly, and the anterior edge is left attached to the periosteum.

A mastoidectomy is performed along with an extended facial recess approach.

The facial nerve is skeletonized.

The bone overlying the posterior and middle fossa dura and the sigmoid sinus is removed.

The semicircular canals are skeletonized.

The integrity of the external auditory canal is preserved.

A craniotome is used to turn a bone flap from the sinodural angle to the zoot of zygoma.

The petrous apex is exposed by elevating the middle fossa dura. The internal auditory canal and the semicircular canals are skeletonized.

The anterior 1/3 of the temporalis muscle is left in place.

The middle 1/3 is inserted into the petrous apex defect.

The posterior 1/3 is used to fill the mastoid and the jugular fossa.

Pts

Age

Sex

Diagnosis Operation

1 8 MGradenigo syndromeTolosa-Hunt Syndrome

Modified circumferential petrosectomy and complete mastoidectomy

2 14 M Gradenigo syndromeModified circumferential petrosectomy

3 66 FAcute mastoiditis with petrous apicitisFacial palsy

Modified circumferential petrosectomyMastoidectomy (zygomatic and supralabyrinthine air cells)

4 84 MCranial base osteomyelitisFacial palsy

Modified circumferential petrosectomy

5 56 FCranial base osteomyelitis

Circumferential petrosectomy

Culture-directed antibiotic therapy as the first-line treatment.

For recalcitrant disease, the circumferential petrosectomy provides the capability to debride the necrotic bone and the inflammatory tissue with a low risk of morbidity.

This procedure can be tailored to the extent of the patient’s disease.

Visosky AMB et al. 2006

Success in the treatment of osteomyelitis elsewhere in the body

Oxidative killing by leukocytes of aerobic bacteria (P. aeruginosa)

In otogenic skull base osteomyelitis, it did not influence disease-specific survival.

Grade I: Mild uptakeGrade II: Focal mastoid/temporal bone uptake not reaching midlineGrade III: Petrous temporal bone uptake reaching midlineGrade IV: Uptake crossing midline to involve the contralateral side

Poor prognostic factors: Fungal / mixed infection Immunocompromised Cranial nerve palsy Intracranial extension

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2. Sreepada GS et al., Skull base osteomyelitis secondary to malignant otitis externa. Curr Opin Otolaryngol Head Neck Surg 2003; 11: 316-323

3. Djalilian HR et al., Treatment of culture-negative skull base osteomyelitis. Otol Neurotol 2006; 27: 250-255

4. Merchant S et al., Osteomyelitis of the temporal bone and skull base in diabetes resulting from otitis media. Skull Base Surg 1992; 2(4): 207-212

5. Petrini B, Non-tuberculous mycobacterial infections. Scad J Infect Dis 2006; 38: 246-255

6. Horwich P, Approach to imaging modalities in the setting of suspected osteomyelitis. Uptodate 2008

7. Coker NJ et al, Atlas of otologic surgery. 1st Ed. Saunders8. Visosky AMB et al., Circumferential petrosectomy for petrous apicitis and

cranial base osteomyelitis. Otol Neurotol 2006; 27: 1003-1013