Perilymphatic Fistula

Etiology

PLFs typically result from mechanical injuries, although some patients may be more predisposed to develop PLFs than others, making predicting what may or may not cause a fistula nearly impossible. The most common etiologies are traumatic and iatrogenic, with roughly 1% of stapes procedures resulting in PLF.[8] Traumatic insults may be pressure-related, eg, a blast injury or even a stifled sneeze, penetrating, as from a foreign body that passes though the tympanic membrane or a cholesteatoma that erodes into the inner ear, or blunt, which may be associated with a temporal bone fracture.[9]

Temporal bone fractures have historically been classified as either longitudinal or transverse, describing the course of the fracture relative to the long axis of the temporal bone's petrous pyramid; longitudinal fractures are more likely to result in conductive hearing loss due to hemotympanum and disruption of the ossicular chain (particularly the incudomalleolar joint), while transverse fractures are more likely to disrupt the otic capsule, causing vertigo and sensorineural hearing loss from the resulting PLF as well as potential facial paralysis.[10][11] PLFs caused by physical exertion like weightlifting, coughing, or sneezing are thought to result from increased cerebrospinal fluid (CSF) pressure that is transferred to the inner ear via the cochlear aqueduct or the internal auditory canal.[12] More unusual causes of PLF reported in the literature include whiplash injuries, lightning strikes, airbag injuries, straining during childbirth, and acoustic trauma from the sirens of emergency vehicles.[3]

PLFs occur in 4% to 15% of cholesteatomas arising from chronic otitis media.[13] The horizontal semicircular canal is the most common location, although other sites within the otic capsule may also be affected.[14] When erosion of the horizontal canal occurs due to cholesteatoma, clinicians should have a high index of suspicion for damage to the facial nerve canal or the tegmen tympani/floor of the middle cranial fossa as well, which occurs in 60% and 39% of cholesteatoma-related PLF.[15] 

Beyond characterizing barotraumatic PLFs as either implosive or explosive, Matsuda and colleagues developed the following classification system for PLFs based on presumed etiology.

• Category 1: PLF etiologies include fistulas resulting from trauma, otologic disease, and otologic surgery
• Category 2: PLFs caused by external barotrauma, either high pressure (eg, diving, blast injury, and boxing the ear) or low pressure (eg, air travel)
• Category 3: Barotrauma from internal sources, eg, coughing, sneezing, and Valsalva maneuvers
• Category 4: PLFs of idiopathic origin [16] 

However, the clinical relevance of this schema is debatable and has not gained wide acceptance.

Epidemiology

Labyrinthine fistulas are rare; their incidence and prevalence are not well characterized, although Fiedler and colleagues estimate a prevalence of 1.5 per 100,000 adults.[17] In cases of chronic otitis media with cholesteatoma, the prevalence of PLFs is reported to range between 4% and 15%.[13] Children with idiopathic hearing loss, on the other hand, may have congenital PLFs in ≥6% of cases.[18] A 2024 study published by Sasaki et al used a biomarker specific for perilymph, cochlin-tomoprotein, to identify PLFs in 22% of sudden sensorineural hearing loss patients, with a higher proportion of elderly patients testing positive.[19] The incidence of PLF is higher in women than in men, potentially as a consequence of the higher incidence of otosclerosis in women, which makes women more likely to undergo stapes surgery.

Pathophysiology

The symptoms PLFs cause can be divided into vestibular and auditory, with disequilibrium occurring approximately twice as frequently as hearing loss.[20] The means by which these symptoms are produced is unclear and may depend on multiple mechanisms. One potential cause is the "third window" effect, in which a dehiscence in the otic capsule bone allows the endosteal membrane that contains the perilymph to vibrate in the same way that the oval and round windows do (see Image. Computed Tomography of Temporal Bones).

While the mobility of the round window is critical to allow vibrations from the stapes footplate and oval window to propagate along the basilar membrane of the cochlea and stimulate the hair cells' stereocilia during normal sound conduction, the addition of a third window, with or without actual leakage of perilymph, may cause loss of vibratory energy in what should otherwise be a closed system, thus resulting in conductive hearing loss. The presence of a third window through which vibratory energy may escape can also alter how fluid waves propagate through the labyrinth, causing sound pressure waves to deflect the cupula of a semicircular canal and produce a sensation of motion or vertigo when no movement is occurring.

Besides the third window effect, imaging of temporal bones with PLFs often shows pneumatosis of the labyrinth, which also impedes fluid wave propagation through the cochlea.[9] Symptom reduction after exploratory tympanotomy and PLF repair has been reported to correspond to radiographically apparent reduction in the volume of air within the labyrinth.[21] The amount of air visible on a patient's imaging may also fluctuate, which is consistent with the often fluctuating nature of PLF patients' symptoms.

According to Black and colleagues, approximately half of PLFs occur at the oval window (52%), with 20% at the round window, and 22% occurring at both sites.[20] Muntarbhorn and Webber further associated the site of the fistula with the reported mechanism, noting that blunt head trauma tends to produce a fistula at the oval window, while barotraumatic and idiopathic fistulas are most likely to develop at the round window.[22]

History and Physical

Clinical History

A thorough history and careful physical examination are critical, as a PLF can easily be overlooked or misdiagnosed. Patients with labyrinthine fistulas complain of hearing loss or disequilibrium, often induced by loud sounds. Aural fullness and autophony, in which patients describe hearing their own voices more loudly than usual, may occur as well.[23] Tinnitus is not commonly encountered with PLFs, although roaring tinnitus has been reported at the onset of symptoms, similar to that described with Ménière disease. While many patients are unable to identify or recall an inciting event that preceded the onset of symptoms, 50% to 80% of patients will.[16]

A labyrinthine fistula should be suspected in patients who sustain temporal bone fracture, penetrating ear injury, or potential barotrauma situations, including the Valsalva maneuver, nose blowing, blast injuries, air travel, and SCUBA diving, before symptom onset.[3] The primary symptoms of a traumatic PLF are sensorineural hearing loss (15%) and dizziness (64%).[14] Symptoms may appear immediately after the inciting event or arise progressively over several days. Additionally, the anatomic defects required to produce PLFs are often so small that they may close spontaneously and recur with minimal additional trauma, leading to fluctuations in symptoms that further hinder diagnosis.

Posttraumatic vestibular dysfunction often presents as disequilibrium, severe vertigo, or positional dizziness.[12] A PLF should also be suspected if a patient has vestibular disturbances or hearing loss after undergoing a stapedectomy. The stapes prosthesis may become dislodged postoperatively, leading to perilymph leakage. Dizziness may also result after stapes surgery; however, it may also result from the inadvertent use of an excessively long prosthesis that contacts and stimulates the vestibular saccule when it vibrates, causing sound-induced vertigo. For this reason, stapes surgery is often performed with the patient conscious during prosthesis placement, thereby permitting the surgeon to ensure the selected prosthesis is of the appropriate length. Finally, a PLF should be suspected in patients with suggestive symptomatology in the setting of chronic otitis media. Development of cholesteatoma may lead to erosion of the otic capsule bone, causing a third window or even a fistula proper, most often where the horizontal semicircular canal protrudes into the mastoid antrum.

Physical Examination

Several physical examination techniques are employed to screen for PLFs. Otoscopy may reveal a cholesteatoma by identifying tympanic membrane retraction or perforation and the presence of squamous debris or a keratin pearl, most often in the posterosuperior portion of the ear drum (see Image. Cholesteatoma). Alternatively, a hemotympanum in the setting of head trauma may indicate a temporal bone fracture, associated clear rhinorrhea likely representing a CSF leak.

The so-called "fistula test" is also easy to employ and will typically elicit a Hennebert sign (evoked nystagmus) if a PLF is present. This maneuver is performed by applying pulsatile pressure to the tragus to induce pressure changes in the external auditory canal, which are then transmitted to the middle and inner ear via tympanic membrane vibrations. Alternatively, air insufflation during pneumatic otoscopy may be more effective. A positive test results in nystagmus, typically accompanied by a sensation of dizziness.

A similar finding is the Tullio phenomenon, in which dizziness and nystagmus occur with exposure to loud sounds. A tuning fork examination should also be performed, which may help identify conductive or sensorineural hearing loss, although audiometry is a more conclusive test.[9] The direction of the nystagmus may help to localize the labyrinthine defect, with horizontal nystagmus alone indicating horizontal semicircular canal involvement and torsional nystagmus with an upward slow phase indicating superior canal dehiscence.[24][25] Horizontal nystagmus with a torsional component whose slow phase beats downward most likely results from posterior semicircular canal dehiscence.[26]

Office-based vestibular testing

Office-based vestibular examination should also include evaluation of the vestibulo-ocular and vestibulo-spinal reflexes. Head shake and head thrust testing will help to identify unilateral vestibular hypofunction by eliciting corrective ocular saccades. The head shake test requires that the patient rhythmically shake their head to the left and the right for several seconds to stimulate the vestibular system bilaterally. Then the examiner tells the patient to stop shaking and quickly bring their head back to midline, looking straight forward at the examiner's nose. Corrective saccades indicate insufficiency of the vestibulo-ocular reflex.

A similar maneuver is the head thrust test, in which the examiner shakes the patient's head back and forth for several seconds before suddenly snapping the head back into midline and asking the patient to look at the examiner's nose; resulting corrective saccades likewise indicate vestibular hypofunction. The Dix-Hallpike test is also typically performed, although this maneuver identifies benign paroxysmal positional vertigo and is an integral part of any complete vestibular assessment. Additionally, the Fukuda/Unterberger test can identify vestibular hypofunction by producing postural instability.[3] The patient is asked to walk forward with eyes closed and then, on command, turn with 1 foot and stop. The test is positive if the patient becomes unsteady after stopping.

Evaluation

Definitively identifying a labyrinthine fistula can be challenging, as no international consensus regarding diagnosis has been established. However, diagnostic criteria has been suggested by the Intractable Hearing Loss Research Committee of the Japanese Ministry of Health and Welfare, which are based on the presence of hearing impairment, aural fullness, tinnitus and disequilibrium in the context of middle/inner ear pathology or barotrauma, with or without visualization of a fistula via tympanotomy or the presence of cochlin-tomoprotein in the tympanic fluid.[16] Patients with suggestive symptoms and history only are considered to have a probable PLF, while additional confirmation via tympanotomy or laboratory studies constitutes a definite PLF.

Audiological Studies 

Numerous audiological studies may be employed to provide additional diagnostic information before undertaking surgical confirmation and repair. Audiometry is needed to determine the type and degree of hearing loss, if any is present, and video or electro-nystagmography will quantify any vestibular hypofunction.[27] Electrocochleography often demonstrates an elevated summating potential (SP) to action potential (AP) ratio if a PLF is present, similar to results in cases of Ménière disease, although the SP increases in Ménière disease, while the AP may decrease with a labyrinthine fistula. 

Electrocochleography is also useful for postoperative follow-up, as the SP/AP ratio typically returns to normal after successful surgical repair of the fistula.[28] Vestibular-evoked myogenic potential testing will likely demonstrate decreased thresholds for sternocleidomastoid contraction from 90 dB down to 70 dB when impulse sounds are presented on the affected side. However, this may be seen in cases of third window phenomena, eg, superior semicircular canal dehiscence as well as PLF.[29] Dynamic platform posturography can be added to standard fistula testing to quantify any imbalance that insufflation of the external auditory canal produces.[30] Swaying as a result of pressure changes in the ear strongly correlates with the presence of a PLF. 

Imaging Studies

With respect to imaging, computed tomography (CT) is the most reliable method for identifying labyrinthine fistula preoperatively, as pneumolabyrinth seen on a CT scan confirms the diagnosis and indicates the need for surgical intervention (see Image. Pneumolabyrinth).[9] If the pneumolabyrinth is very small, however, visualization on CT may be improved with coronal views of the temporal bone because the air tends to rise to the top of the semicircular canals, which are well visualized from this perspective.[9] 

Other advantages of CT scanning are that it is particularly adept at characterizing the extent of cholesteatoma erosion of the otic capsule bone and revealing congenital anomalies of the inner ear that can increase the risk of PLF, including enlarged vestibular (>1 mm) and cochlear aqueducts, and Mondini deformities (see Images. Cholesteatoma CT, Enlarged Vestibular Aqueduct, and Mondini Deformity).[31] The sensitivity of CT scanning alone for identification of a PLF is >80%, while that of CT and magnetic resonance imaging combined approaches 100%.[14][32]

Invasive Diagnostic Evaluation

Invasive evaluation for labyrinthine fistula may be performed via transtympanic endoscopy, either as the first step of exploratory tympanotomy or as an office-based procedure. A radial myringotomy is made, with topical phenol anesthesia if the patient is awake, and a small (1.9 mm), rigid endoscope is introduced to visualize the oval and round windows. Because PLFs may be intermittent, a finding of clear fluid at the oval or round window may not be present at the time of evaluation.

For this reason, some surgeons advocate using the Valsalva maneuver to provoke perilymph leakage, although this may increase the risk of hearing loss. Despite the high-quality view of the middle ear provided by endoscopy, findings often differ from those encountered with formal exploratory tympanotomy, even when surgery is performed immediately after the endoscopy.[33][34] Endoscopy does, nevertheless, retain one advantage: its ability to obtain fluid samples for preoperative analysis, permitting identification of cochlin-tomoprotein and potentially β-2 transferrin as well.

Use of β-2 transferrin to confirm the presence of perilymph remains controversial though, as assays are unlikely to detect it in the extremely small sample volumes obtained from the middle ear unless the assays are highly sensitive; the highly sensitive assays, however, are liable to detect the protein even in serum, which may contaminate middle ear fluid samples.[35][36] More recently, flexible endoscopy via the Eustachian tube has been used to visualize the middle ear cleft without requiring a myringotomy, although the views of the oval and round windows this technique provides are generally inferior to those provided by transtympanic endoscopy.[37]

Treatment / Management

Nonsurgical Management

Because of a lack of definitive diagnostic criteria, conservative management is preferred initially with head elevation, bed rest, and avoidance of straining, lifting heavy objects, and other activities that increase intracranial pressure. If symptoms persist or are recurrent, an intratympanic blood patch or exploratory tympanotomy would be the next step. Surgery has been shown to decrease vestibular symptoms reliably but rarely improves hearing, sometimes even resulting in iatrogenic sensorineural hearing loss.[13][12] 

On the other hand, the blood patch procedure is performed in the office and requires only 0.5 mL of the patient's blood injected into the middle ear, followed by maintaining a supine position for half an hour.[38] As with an epidural blood patch, the intratympanic procedure likely creates a mechanical and inflammatory seal at the round and oval windows. Blood patching has a high success rate, although symptomatic relief is only temporary for some patients. If the blood patch improves the symptoms, but they relapse, the patient is likely a good candidate for tympanotomy; however, if the blood patch produces no symptomatic improvement, the diagnosis of labyrinthine fistula may be called into question.[21]

Surgical Management

Currently, no consensus exists on the optimal surgical management of labyrinthine fistula.[13] Goto et al concluded that urgent tympanotomy was unnecessary due to poor hearing outcomes.[39] Seltzer and McCabe, however, found that hearing improvement was still possible with repair even after many years of symptoms.[40] While the role of operative intervention in cases of idiopathic PLF remains unclear, surgery is more widely accepted as appropriate for PLFs with known causes, with earlier intervention preferred to prevent the progression of hearing loss.[41] (B3)

Repair of labyrinthine fistula in the middle ear is classically accomplished via a tympanotomy, using a postauricular approach. This involves elevating a tympanomeatal flap with incisions in the posterior aspect of the external auditory canal and reflection of the skin-tympanic membrane flap anteriorly to expose the posterior aspect of the middle ear, including the ossicles, the chorda tympani nerve, and the round window.

Curettage of the posterosuperior bony scutum permits translocation of the chorda tympani and wider visualization of the stapes footplate. Inspection of the footplate and round window niche may reveal clear fluid, which can be indicative of a PLF; however, these concavities may also collect mucous transudate and local anesthetic solution, making it difficult to identify perilymph without laboratory confirmation of β-2 transferrin or cochlin-tomoprotein, which cannot be performed with a rapid assay suitable for intraoperative use.[33]

While increasing intracranial pressure via the Valsalva maneuver may make perilymph leakage more visually apparent, it should be avoided due to the danger of causing additional hearing loss.[20] Regardless of whether or not a fistula is visualized, the majority of surgeons will use temporalis fascia, parotid fascia, or tragal perichondrium to reinforce the round and oval windows during every exploratory tympanotomy for PLF (see Image. Standard Surgical Techniques of Perilymph Fistulas Repair).[42] Before the placement of the grafts, the mucosa should be denuded to improve adhesion.(B3)

Any fascial grafts placed onto the oval window should be very thin to avoid causing conductive hearing loss by dampening stapes footplate vibrations. Fat grafting is avoided entirely because it is less likely to prevent the recurrence of a fistula in the long term.[21] Some surgeons advocate the use of endoscopic tympanotomy over an open approach with a microscope due to its less invasive nature, higher magnification, and wider field of view. However, using an operating microscope provides better depth perception and the ability to operate with 2 hands simultaneously, as one hand is not occupied while the endoscope is being operated.[23](B2)

Corticosteroids administered intravenously during surgery have been associated with better hearing outcomes, and they may also be injected intratympanically in the office during episodes of acute vertigo. Obliteration of the mastoid has also been reported to improve postoperative dizziness in some patients, particularly those with cholesteatoma-induced erosion of the horizontal semicircular canal.[13] 

Management of labyrinthine fistula due to penetrating trauma or cholesteatoma requires not only repair of the leak itself but also removal of the offending pathology. In the case of cholesteatoma, this requires complete extirpation of the matrix and resurfacing of the bony defect with fascia, cartilage, bone pâté, or bone chips, typically at the horizontal semicircular canal but potentially at the oval window or the cochlear promontory as well.[13]

Differential Diagnosis

Differential diagnoses for concomitant vertigo and hearing loss include:

• Ménière disease/primary endolymphatic hydrops (more common than PLF and can present with similar symptoms)
• Secondary endolymphatic hydrops (due to head trauma, allergy, or autoimmune disorders such as Cogan disease) [43][13]
• Medication ototoxicity (cochleotoxicity or vestibulotoxicity, most commonly from aminoglycoside antibiotics, antineoplastic agents, loop diuretics, and aspirin)
• Acoustic neuroma (vestibular schwannoma)
• Labyrinthitis
• Vestibular neuronitis
• Vestibular migraine
• Semicircular canal dehiscence
• Enlarged vestibular aqueduct
• Enlarged cochlear aqueduct

Prognosis

Surgical intervention has been shown to improve vestibular symptoms more than hearing loss, the latter of which may or may not improve with surgical intervention.[44] However, some evidence has demonstrated that the prognosis for improvement of symptoms correlates inversely with the magnitude of the inciting event and the severity of symptoms at onset.[12] 

The more severe the symptoms or the more traumatic the inciting events, the less likely a spontaneous resolution will occur or surgical intervention will succeed. Improvement in hearing after exploratory tympanotomy and fistula repair was reported to only be 9% to 17% from the data collected by Goto's and Black's groups. However, with early repair, resolution of vestibular symptoms is very likely, and hearing improvement may occur in up to half of patients.[39][20]

Complications

The most common complications of PLFs themselves are hearing loss and vertigo. However, when a fistula occurs due to a congenital inner ear anomaly, recurrent meningitis may be the presenting complaint due to an abnormal connection between the middle ear and the CSF-containing spaces.[45][46] Complications may also occur with fistula repair. These include tympanic membrane perforation due to traumatic tympanomeatal flap elevation, postoperative conductive or sensorineural hearing loss, and chorda tympani nerve injury with resulting taste loss or dysgeusia.[47] Fortunately, postoperative hearing loss and chorda tympani injury are temporary in many patients, lasting only a few months.[16]