Perilymphatic fistula

By Marcello Cherchi, MD PhD

For patients

A perilymphatic fistula (PLF) is an abnormal hole connecting the inner ear and the middle ear. It often results from trauma. It presents with hearing symptoms (hearing loss, excessively sensitive sound, tinnitus) and disequilibrium. Symptoms are often worsened by pressure changes (e.g., sneezing, coughing) or by exposure to a burst of loud sound. The most confident way to diagnosis PLF is at surgery, during which the surgeon actually visualizes fluid coming out of the abnormal hole connecting the inner ear and middle ear. Other ways of testing for PLF have not been as successful. Treatment is surgery by an otolaryngologist. Surgery is not always successful, and even when surgery is initially successful, PLF can recur.

For clinicians

Overview

A perilymphatic fistula (PLF) is an abnormal connection between the inner ear and the middle ear via a hole in the oval window or round window or both.  It is often caused by trauma of various sorts, and can occur at any age.  It presents with aural, auditory and vestibular symptoms, often triggered or exacerbated by pressure changes (e.g., Valsalva, diving) or by loud noises.  Visualization of the fistula at surgery is the best way to secure the diagnosis.  Other testing modalities (imaging, otovestibular testing, assays on middle ear fluid) are inferior to surgical exploration.  PLF should be differentiated from labyrinthitis, Ménière’s disease and semicircular canal dehiscence.  Treatment of PLF is surgical repair, though it is not always successful.  Even when surgical repair is initially successful, PLF can recur.

Introduction

Perilymphatic fistula (PLF) is a condition in which an abnormal communication (essentially, a hole) develops in either the oval window, or the round window, or both. This abnormal communication between the inner ear and the middle ear permits vestibular and cochlear hair cells to be stimulated abnormally, manifesting as various combinations of auditory and vestibular symptoms. There are numerous potential causes; it appears that the majority of cases occur following trauma. Diagnosis is difficult; surgical exploration (enabling the surgeon to visualize the middle ear) remains the best way to secure the diagnosis, but is obviously invasive. Limited studies suggest that imaging may play some role. Other tests (audiologic, otovestibular, blood tests) are controversial and not widely accepted. Some PLFs heal spontaneously; in other cases surgery may be curative, but is not always successful.

Epidemiology

Because it is difficult to diagnose PLF, the diagnosis is controversial. Consequently it has been difficult to arrive at useful statistics regarding its incidence and prevalence.

PLF can occur at any age; it can be congenital (Reilly 1989, Reilly and Kenna 1989, Weber, Perez et al. 1993, Weissman, Weber et al. 1994, deJong 1998); it can occur in the pediatric population (Healy, Friedman et al. 1978, Pappas, Simpson et al. 1988, Ruben and Yankelowitz 1989, Weber, Kelly et al. 1994, Kim, Kazahaya et al. 2001, Nakashima, Sone et al. 2003, Rawal, Zhao et al. 2021), in young adults (Fitzgerald 1996), in middle and older age.

Pathophysiology

An understanding of PLF requires some brief comments on anatomy, hydraulics and physiology.

The interface between the inner ear and the middle ear consists of the oval window (to which the stapes footplate is attached) and the round window; both of these “windows” are covered by a soft membrane that can bulge inward or outward. Vibrations (typically from sound) cause an oscillating (inward and outward) piston-like motion of the stapes footplate. If the oval window were the only interface, then the stapes would barely be able to move the round window because inner ear fluid is effectively incompressible. However, the round window oscillates in a direction opposite that of the oval window; in other words, when the stapes pushes the oval window inwards, the round window bulges outwards, and vice versa. This arrangement makes it possible for vibration of the stapes footplate to be transduced into movement of the perilymph/endolymph and propagate through the labyrinth, usually stimulating hair cells in the cochlea which gets perceived as sound.

If the integrity of the oval window or round window is disrupted, then the overall resistance of the system (in a hydraulic sense) is reduced. There are several consequences to this reduced resistance.

• First, it will be easier to stimulate the inner ear with regular stimuli (such as sound). This can lead to perceiving sounds as louder in the affected ear.
• Second, the labyrinth may be stimulated by phenomena that would not normally do so. This can lead, for example, to auditory and vestibular symptoms triggered by Valsalva (such as during coughing, sneezing, etc.).
• Third, hair cells that are not normally stimulated by sound (specifically, vestibular hair cells) may get stimulated. This can lead to Tullio’s phenomenon.

PLF can involve the oval window, or the round window, or both, as illustrated in the Figure below.

Etiology

PLF has been reported in a broad variety of circumstances. The majority of cases reported occur in the context of some sort of trauma (Fee 1968, Lehrer, Poole et al. 1980, Glasscock, Hart et al. 1992, Fitzgerald 1995, Kim, Kazahaya et al. 2001, Gunesh and Huber 2003, Whitelaw and Young 2005, Nishiike, Hyo et al. 2008, Tsubota, Shojaku et al. 2009, Khoo and Tan 2011, Prisman, Ramsden et al. 2011, Fife and Giza 2013, Osetinsky, Hamilton et al. 2017, Kita, Kim et al. 2019, Rawal, Zhao et al. 2021, Koksal, Ayyildiz et al. 2022).  A non-exhaustive list of potential etiologies is shown below.

Various sorts of trauma

• Barotrauma (Pullen 1992, Sheridan, Hetherington et al. 1999, McGhee and Dornhoffer 2000, Shupak 2006, Ahn, Son et al. 2019), particularly diving (Sheridan, Hetherington et al. 1999, Shupak 2006, Morvan, Gempp et al. 2016).
• In the context of the “common cold” (Klokker and Vesterhauge 2005), during which presumably a person is coughing and/or sneezing.
• Sneezing (Comacchio and Mion 2018).
• Nose blowing (Lee, Kwon et al. 2015).
• Vehicular airbag trauma (Ferber-Viart, Postec et al. 1998).
• Cotton swab use (Smith, Darrat et al. 2012).
• Stapes luxation (Hatano, Rikitake et al. 2009, Khoo and Tan 2011).
• Whiplash (Markou, Rachovitsas et al. 2014).
• Lightning strike (Sun, Simons et al. 2006, Kilic, Genc et al. 2017).

Pathologies that can potentially erode into the inner ear

• Cholesteatoma (Gormley 1986, Magliulo, Terranova et al. 1997).
• Granuloma (Kuhweide, van de Steene et al. 2007).
• Mastoiditis (McCabe 1984).
• Otitis media (Bluestone 1988).

Surgical complications

• Complication of stapes surgery (Albera, Canale et al. 2004).
• Complication of surgical drilling elsewhere in the temporal bone (Tsunoda, Anzai et al. 2021).
• Complication of transtympanic injection (Qureshi and Zeitler 2021).
• Migration of tympanostomy tube (Hajiioannou, Bathala et al. 2009).

There is a somewhat contentious discussion in the literature regarding whether PLF can also occur spontaneously (Pashley and Shapiro 1978, Ruben and Yankelowitz 1989, Gibson 1993, Meyerhoff 1993, Cole 1995, Kohut, Hinojosa et al. 1995, Kohut, Hinojosa et al. 1995, Collison and Pons 2004).

Clinical presentation

PLFs usually present with some combination of aural symptoms (e.g., fullness), auditory symptoms (hearing loss, hyperacusis, tinnitus) and vestibular symptoms (disequilibrium).

The symptoms often have episodic exacerbations, sometimes precipitated by pressure changes, whether internally generated (e.g., Valsalva while sneezing, coughing, blowing the nose, straining at stool) or externally generated (e.g., airplane ascent/descent, diving).

In some cases the symptoms are chronic, though in such cases the baseline symptoms are generally punctuated by acute exacerbations, as described earlier.

Diagnosis: physical examination

Often physical examination is normal. However, in some cases it may be possible to observe a bedside Tullio’s phenomenon by presenting a loud noise that elicits an ocular motor response (usually an oscillatory nystagmus). In other cases it may be possible to increase middle ear pressure (either with a pneumatic otoscope, or by applying pressure on the tragus) and observe nystagmus (Casale, Errante et al. 2014).

Diagnosis: imaging

Since PLF involves a very small hole in very small structures, it is difficult for this to be captured on contemporary imaging. Nevertheless, a number of studies and case series have collected radiographic observations (Nakashima, Sone et al. 2003, Ehmer, Booth et al. 2010, Venkatasamy, Al Ohraini et al. 2020), with some focusing on CT (Weissman, Weber et al. 1994, Kvestad, Kvaerner et al. 2001, Bozorg Grayeli, Bensimon et al. 2020) and others focusing on MRI (Morris, Kil et al. 1993, Algin, Bercin et al. 2012, Dubrulle, Chaton et al. 2020).

Diagnosis: audiologic and vestibular testing

A variety of otovestibular tests have been explored for the diagnosis of PLF, including:

• Audiometry (Fukaya and Nomura 1988) and “positional audiometry” (Hazell, Fraser et al. 1992).
• Electrocochleography (Arenberg, Ackley et al. 1988, Campbell and Parnes 1992, Campbell and Savage 1992, Campbell, Savage et al. 1992, Gibson 1992, Morris 1994, Sass, Densert et al. 1997) and “positional electrocochleography” (Campbell and Abbas 1993, Campbell and Abbas 1994).
• Otoacoustic emissions (Kokesh, Norton et al. 1994).
• Vestibular evoked myogenic potentials (Suzuki, Kitajima et al. 2003, Modugno, Magnani et al. 2006).
• Caloric testing (Dapsit, Churchill et al. 1980, Suzuki, Kitajima et al. 2003).
• Computerized dynamic posturography (Black, Lilly et al. 1990, Shepard, Telian et al. 1992, Selmani, Ishizaki et al. 2004, Pyykko, Selmani et al. 2012).

Ultimately, none of these methods has been widely accepted as diagnostic of PLF.

Diagnosis: laboratory tests on middle ear fluid

Although surgery remains considered the best way to diagnose PLF, sometimes the surgeon will not find clear evidence of PLF intraoperatively (Aso and Gibson 1994, Morris 1994, Haubner, Rohrmeier et al. 2012). On the possibilities that a fistula is very small, or has recently healed, some efforts have been directed at laboratory assays for fluid found in the middle ear at surgery with the goal of confirming/refuting the clinically suspected diagnosis of PLF. The main assays that have been studied are for beta-2-transferrin (Bassiouny, Hirsch et al. 1992, Skedros, Cass et al. 1993, Weber, Kelly et al. 1994, Weber, Bluestone et al. 1995, Delaroche, Bordure et al. 1996, Bluestone 1999), beta trace protein (Michel, Petereit et al. 2005, Bachmann-Harildstad, Stenklev et al. 2011) and cochlin-tomoprotein (Kataoka, Ikezono et al. 2013, Matsuda, Sakamoto et al. 2017, Fujita, Kobayashi et al. 2019, Lee, Ochi et al. 2020). None of these has been widely accepted.

Diagnosis: surgery

Surgery remains the gold standard for diagnosing PLF (Sekula and Wlodyka 1982, Yanagihara and Nishioka 1987, Poe, Rebeiz et al. 1992, Harvey and Millen 1994, Ogawa, Kanzaki et al. 1994, Poe and Bottrill 1994, Selmani, Pyykko et al. 2002, Alzahrani, Fadous et al. 2015, Prenzler, Schwab et al. 2018, Heilen, Lang et al. 2020). In this case, “surgery” means accessing the middle ear space either by myringotomy or by endoscopy, and observing the oval and round windows to detect whether fluid is seeping from them. While this remains the gold standard, it is imperfect, in that (1) it is invasive; and (2) many cases of clinically suspected PLF show no evidence of it during surgery (Aso and Gibson 1994, Morris 1994, Haubner, Rohrmeier et al. 2012).

The Figure below is a photograph of an endoscopic procedure visualizing perilymphatic leak from the anterior oval window from Rawal and colleagues (Rawal, Zhao et al. 2021).

Diagnosis: differential diagnosis

A number of diseases besides PLF can cause auditory and vestibular symptoms. While the differential diagnosis can be broad, the main considerations include:

• Chronic symptoms from PLF can be difficult to differentiate from labyrinthitis.
• Episodic symptoms from PLF can be difficult to differentiate from Ménière’s disease (Arenberg, May et al. 1974, Fitzgerald 2001).
• Chronic and episodic symptoms from PLF can be difficult to differentiate from semicircular canal dehiscence (Weinreich and Carey 2019).
• PLF can co-exist with other otologic pathologies, such as lateral semicircular canal dehiscence (Yaniv, Hacking et al. 1986, Yaniv and Hacking 1987).

Treatment

Surgical repair of PLF remains the mainstay of treatment (Lehrer, Rubin et al. 1984, Palva and Ramsay 1989, House, Morris et al. 1991, Black, Pesznecker et al. 1992, Deguine, Latil d’Albertas et al. 1995, Fitzgerald, Getson et al. 1997, Weider 1997, Maitland 2001, Weber, Bluestone et al. 2003, Kimitsuki, Hara et al. 2004, Omichi, Kariya et al. 2018, Ahn, Son et al. 2019, Rawal, Zhao et al. 2021). However, it must be kept in mind that surgery is not always successful (Heilen, Lang et al. 2020), and even if surgery is initially successful, PLF can recur (Gyo, Kobayashi et al. 1994).

Given that surgery is invasive and not always successful, a number of other treatments have been investigated, including autologous blood patch(Garg and Djalilian 2009, Foster 2016) and ventriculoperitoneal shunt (Weider, Roberts et al. 2005, Lollis, Weider et al. 2006). However, none of these has had the same rate of success as surgery.

Prognosis

Prognosis of PLF, both treated and untreated, is quite variable (Kubo, Kohno et al. 1993, Weber, Bluestone et al. 2003, Tsubota, Shojaku et al. 2009), and often these patients have long-term follow-up with an otolaryngologist.

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