Continuing Education Activity

Labyrinthitis is an inflammation of the membranous labyrinth of the inner ear and typically presents with vertigo, nausea, vomiting, tinnitus, and/or hearing impairment/ loss. It is normally caused by a bacterial or viral infection. However, in some cases, it can be a manifestation of systemic autoimmune disease or HIV. Although most patients make a complete recovery, in some cases, patients may be left with residual balance or hearing problems. This activity reviews the evaluation and treatment of labyrinthitis and highlights the role of the interprofessional team in evaluating and treating patients with this condition.

Objectives:

• Identify the different causes of labyrinthitis.
• Explain the common examination findings associated with labyrinthitis.
• Summarize the treatment options for the different etiologies of labyrinthitis.

Introduction

Labyrinthitis is an inflammation of the membranous labyrinth of the inner ear and typically presents with vertigo, nausea, vomiting, tinnitus, and/or hearing impairment/ loss.[1] There is little epidemiological data about labyrinthitis, however, the incidence seems to increase with age.[2] Many other serious conditions can mimic the symptoms of labyrinthitis, such as a cerebrovascular accident (CVA), which is why it is crucial to perform a thorough history, examination, and investigations before diagnosing labyrinthitis. It is normally caused by a bacterial or viral infection, however, in some cases, it can be a manifestation of systemic autoimmune disease or HIV.[3][4] Treatment is tailored to the etiology and symptom control. Although most patients make a complete recovery, in some cases, patients may be left with residual balance or hearing problems.

Anatomy

The inner ear consists of two structures: the bony labyrinth and the membranous labyrinth. The bony labyrinth is a collection of bony cavities situated within the temporal bone of the skull. It has three main parts, the vestibule, cochlear, and three semi-circular canals.[5] All three of these structures contain a substance known as perilymph.[6] The membranous labyrinth is located within the bony labyrinth and consists of four structures: the saccule, utricle, semi-circular ducts, and cochlear duct. These are all filled with a substance known as endolymph. The inner ear itself has two connections with the middle ear and two connections with the central nervous system. The oval window connects the vestibule to the middle ear, and the round window connects the cochlear duct to the middle ear. Whereas the internal auditory canal and cochlear aqueduct connect the inner ear and central nervous system (CNS).[6]

Etiology

Labyrinthitis is an inflammation of the membranous labyrinth. It can be caused by viruses, bacteria, or systemic disease.[3] In a rare number of cases, it can result in  Labryrinthitis ossificans, pathological new bone formation within the membranous labyrinth.[7] Vestibular neuritis is often used interchangeably with labyrinthitis. However, technically this term can only be used when just the vestibular nerve is involved.[8] 

Viral Labyrinthitis

The most common cause of labyrinthitis is secondary to a viral upper respiratory tract infection. Labyrinthitis secondary to maternal rubella or cytomegalovirus infections is one of the most common causes of congenital deafness, while in the post-natal period mumps and measles, are the leading causes of viral hearing loss.[9][10][11][12] Ramsay-Hunt syndrome, also known as herpes zoster oticus, is caused when a latent varicella-zoster virus infection becomes reactivated, often years after the primary viral infection.[13] This classically produces a vesicular rash, usually in the oral mucosa or ear, along with peripheral facial nerve paralysis. The virus can also involve vestibular and cochlear nerves in 25% of cases.[14] Finally, although the exact etiology of sudden sensorineural hearing loss (SNHL) remains unknown.[15] some research points towards a CMV inflammatory protein-mediated cause.[16] 

Bacterial Labyrinthitis

Bacterial labyrinthitis typically arises from either bacterial meningitis (20% of children with bacterial meningitis will develop auditory or vestibular symptoms) or otitis media.[17][18] The inflammation can occur via two different mechanisms. In serous labyrinthitis, the inflammation is secondary to bacterial toxins and/or host cytokines and inflammatory mediators.[19] Suppurative labyrinthitis, on the other hand, is inflammation caused directly by the bacteria. This will have entered the inner ear through the aforementioned oval window or round window, which connects the inner ear to the middle ear or via the central nervous system through the cochlear aqueduct or auditory canal. The round window is the most common entry point. They may also arise from acquired and congenital defects in the bony labyrinth.[5]

Autoimmune Labyrinthitis

Labyrinthitis has been demonstrated to be a rare complication of both polyarteritis nodosa and granulomatosis with polyangiitis.[20][21]

HIV/ Syphilis

Both syphilis and HIV have been associated with labyrinthitis. However, there is limited research as to whether the inflammation is caused by opportunistic infections as a result of the HIV related immunosuppression or the virus itself.[22]

Epidemiology

There is little research into the incidence and prevalence of labyrinthitis, however, in South Korea, the prevalence of vestibular dysfunction varied from 3.1% to 35.4%, and the incidence increased with age.[2] Viral labyrinthitis is the most common form and is usually secondary to an upper respiratory tract infection.[3] It typically presents in adults aged 30-60 and is twice as common in females.[23] Suppurative bacterial labyrinthitis, as a complication of bacterial meningitis, is the commonest cause of deafness in children under 2, however, fortunately, this is vanishingly rare in the post-antibiotic era. Otogenic Suppurative labyrinthitis can occur at any age and is typically found in the presence of cholesteatoma or secondary to untreated otitis media.[19][24]

History and Physical

When taking a history from a patient with suspected Labyrinthitis it is important to screen for risk factors. These include recent viral infections (commonly upper respiratory tract infections), cholesteatoma, meningitis, and acute/chronic otitis media.

• Nausea, vomiting and severe ‘room spinning’ vertigo are the most common symptoms.[1] Initial vertigo rarely lasts longer than 72 hours, however, balance issues and occasional brief episodes of vertigo may persist for a number of weeks.
• Patients may also complain of hearing loss or tinnitus, this clinically differentiates labyrinthitis from vestibular neuritis, which is not associated with any auditory symptoms.[19]
• Targetted questioning regarding neurological symptoms such as numbness, weakness, dysphagia, dysarthria, and facial pain is crucial as these could indicate a CVA affecting the brain stem.[4]
• It is also important to clarify the number of episodes of ‘room-spinning’ vertigo. If it has occurred more than once then Meniere disease must also be amongst the differentials.[25]

On examination, patients will often display nystagmus, the fast phase will move away from the affected ear. Patients may also present with gait and balance disturbances, therefore, both Romberg’s test and tandem gait are key to a complete examination. Rinne and Weber hearing tests will likely demonstrate sensorineural hearing loss in the affected ear. Otoscopy may give clues to the etiology of the disease e.g otitis media, cholesteatoma. A full neurological examination should be performed including cerebellar and meningeal tests. Finally, if querying bacterial meningitis be sure to fully examine the patient for the classical non-blanching rash.[26]

Evaluation

Audiometry is useful to confirm examination findings and assess the extent of the sensorineural hearing loss. Specific investigations into the vestibular system (e.g., evoked myogenic potentials, electronystagmography, and rotary chair tests) are not indicated in the acute phase of the disease. However, they can be useful in assessing long term compensation and residual deficits.

The laboratory tests should be tailored to the patients’ symptoms and differential diagnosis. If the patient presents with severe vomiting, then a urea and electrolytes panel should be performed to assess whether electrolyte replacement needs to be initiated. If bacterial meningitis is suspected, then CSF cultures should be sent. Subsequently, consider HIV and Syphilis serology in high-risk individuals or atypical presentations. Finally, consider autoimmune screens in patients with systemic symptoms or atypical presentations with negative serology.

MRI/ CT imaging may be useful. For example, 13% of acoustic neuromas present with sudden hearing loss, which can be diagnosed using an MRI. Gadolinium-enhanced magnetic resonance imaging (GdMRI) is extremely accurate in predicting if a patient with bacterial meningitis will subsequently develop hearing loss, a complication in 14% of cases.[27][28][29]

Treatment / Management

Treatment must be tailored to the etiology and symptoms. Viral labyrinthitis should principally be managed by hydration and bed rest in the outpatient setting. However, it is crucial that patients are given safety netting advice to seek further medical help if their symptoms deteriorate, or they experience any neurological disturbances (e.g., weakness/numbness, diplopia, slurred speech, and gait disturbance).[30] There is currently little evidence around the use of antiviral medications and steroids.[31][32]

In bacterial labyrinthitis, antibiotic type and route depend on the source. For example, if it is secondary to otitis media, then topical antibiotic drops should be prescribed. The ear must be cleaned if the patient has purulent otorrhea or tympanic membrane perforation. However, if the patient has systemic symptoms, consider oral or even intravenous antibiotics, depending on the severity of the infection. If bacterial meningitis is queried, then treat immediately with intravenous antibiotics. A concurrent otogenic source should still be ruled out, and topical, and IV antibiotics can be given simultaneously if appropriate.

The initial management of autoimmune labyrinthitis is corticosteroids. If patients are refractory to corticosteroid therapy, then other immunomodulators may be considered, such as azathioprine, etanercept, or cyclophosphamide. These agents are often used in chronic conditions due to their reduced side effect profile when compared to corticosteroids. However, this treatment should be overseen by a specialist.[33] If a patient’s serology is positive for syphilis or HIV, they should be started on the appropriate treatment and referred to a specialist.[34]

Whilst suffering from initial vertigo, patients will want to lie motionless with their eyes closed. it is important that they attempt to mobilize as soon as possible (even if this exacerbates their vertigo) as this is believed to help with vestibular compensation and prognosis.[35]

Benzodiazepines and antihistamines can be used to treat initial vertigo. However, symptoms should not persist for longer than 72 hours. Therefore, only short courses of these medications should be prescribed as they can inhibit vestibular compensation. Antiemetics, such as prochlorperazine, should be used to help control nausea and vomiting. Whilst patients with sudden hearing loss should receive a course of corticosteroids and be referred to a specialist.

A small minority of patients may be left with tinnitus. It is important to recognize the relationship between this and reactive depression and intervene early with treatments such as tinnitus re-training, tinnitus maskers, hearing aids, and/or biofeedback.[36][37]

Surgical intervention is only required in a minority of cases, for example, mastoidectomy in patients with cholesteatoma or severe mastoiditis. Occasionally patients may require drainage of effusions or myringotomy in labyrinthitis secondary to otitis media.

Once the acute labyrinthitis has resolved, patients may be left with persistent vestibular symptoms, which can seriously impact their life.[38] These patients should be referred for vestibular rehabilitation.[39]

Differential Diagnosis

•  Vestibular Neuritis: This has a similar presentation to Labyrinthitis without the hearing loss.[40]
•  Meniere disease: This also causes hearing loss and vertigo; however, the episodes are usually intermittent.[41]
•  Benign positional vertigo: This causes dizziness but not hearing loss, and patients will have a positive Dix-Hallpike test.[42]
•  Posterior fossa CVA: If a patient presents with any neurological signs, ataxia, hoarseness dysarthria, or dysphagia, a CT/MRI head should be requested immediately to rule out a CVA.[43]
•  Acoustic neuromas/ vestibular schwannomas: These can be visualized using a GdMRI.[44]
•  Inner ear malformations, e.g. (missing crura of the stapes, atresia, abnormal incus): This typically presents with progressive hearing loss and can be diagnosed using CT or MRI imaging.[45]
•  Temporal bone fracture: This should be considered if there is a recent history of head trauma and can be confirmed with CT imaging.[46]
•  Inner ear hemorrhage: Commonly associated with trauma and easily demonstrated on MRI.[47]
•  Temporal bone neoplasm: Usually presents with cranial nerve deficits or facial paralysis and should be investigated with MRI and/or CT.[48]
•  Multiple sclerosis: This is more likely to present alongside other systemic symptoms such as spasticity or signs of optic neuritis.[49]

Pertinent Studies and Ongoing Trials

Superoxide dismutase has been shown to limit the hearing loss and prevent Labyrinthitis Ossificans in gerbils with bacterial meningitis, and TNF-alpha inhibitors appear to reduce postmeningitic cochlear injury and hearing loss.[50][51] There is also some evidence suggesting that corticosteroid therapy in pneumococcal meningitis may prevent labyrinthitis ossificans and research into intra-tympanic corticosteroids as a superior therapeutic administration route have also shown promising results.[52] Finally, cochlear microperfusion and antioxidant therapy have shown some potential as adjuvant therapies.[53][54][55]

Prognosis

The acute vertigo of labyrinthitis should resolve within a couple of days; however, milder symptoms may persist for a number of weeks. Provided the patient had no serious neurological sequelae, the prognosis is usually good. However, patients with neurological complications may require further interventions. For example, ventriculoperitoneal shunts in patients with hydrocephalus secondary to bacterial meningitis.[56] Patients who receive a prolonged course of benzodiazepines and/or antihistamines to treat their vertigo appear to have delayed vestibular recovery. In contrast, suppurative labyrinthitis is more likely to cause permanent hearing impairment.

Complications

Bilateral vestibular hypofunction is a debilitating complication associated with bilateral labyrinthitis, most commonly caused by bacterial meningitis. It can result in visual impairment (Oscillopsia) and impaired spatial awareness often leaving patients reliant on mobility aids.[57] After severe cases of labyrinthitis, some patients may be left with hearing loss or tinnitus which can be managed with a hearing aid or tinnitus specific therapies.[36] 

Complete deafness is a rare complication of bilateral labyrinthitis, usually caused by bacterial meningitis. Labyrinthitis ossificans is recognized as a complication of suppurative labyrinthitis.[58] If bacterial labyrinthitis is not treated effectively there is the risk of it developing into mastoiditis. This typically responds well to IV antibiotics, however, it can result in mastoidectomy with tympanoplasty in severe cases.[59] Finally, labyrinthectomy may be required to terminate the disease process in rare cases of Labyrinthitis secondary to cholesteatoma.[59]

Deterrence and Patient Education

Labyrinthitis is often secondary to another infection, such as otitis media or meningitis. Therefore early diagnosis and effective management of these should prevent the development of labyrinthitis or at least minimize the risk of long term complications. It is also key that populations are up to date with their vaccinations to reduce the risk of contracting measles, mumps, or rubella.

Enhancing Healthcare Team Outcomes

The interdisciplinary team is crucial in delivering optimum care for a patient with labyrinthitis. Firstly, it is key that primary and secondary care doctors are well aware of both the signs and symptoms of labyrinthitis and the other common/ serious differentials diagnoses. This will ensure that the patient receives prompt and effective management, and potentially life-threatening conditions that can mimic labyrinthitis, such as cerebellar CVA, are not missed. 

Both nurses and pharmacists are key in the initial management of a patient with labyrinthitis and, therefore, must have a good understanding of the condition. For example, nursing staff must be aware that the patient could be at high risk of falls and may need assistance with transfers due to their vertigo. They may also take a lot longer completing tasks and, therefore, should not be rushed. Pharmacists should provide advice on the most appropriate medications to help treat the patient’s symptoms, e.g., nausea, and vertigo. For example, the use of benzodiazepines and antihistamines to manage acute vertigo should only be prescribed short term as they can hinder vestibular recovery. They should also be aware of medications that can cause symptoms that mimic those of labyrinthitis when taking a drug history, as this is a cause that is occasionally overlooked.

Patients can be left with residual vestibular symptoms, which severely impact their quality of life. This is when input from both occupational and physiotherapists is essential. Occupational therapists can perform assessments of the home environment and implement changes to improve patient safety and maintain quality of life. Whilst physiotherapists can offer vestibular rehabilitation. After 1 or 2 sessions of vestibular rehabilitation, symptoms can be significantly improved or may be eliminated altogether.