Abstract
Meniere’s disease (MD) is characterized clinically by episodic vertigo, fluctuating hearing loss, and tinnitus, and histologically by the presence of endolymphatic hydrops seen on postmortem examination. MD continues to be a diagnostic and therapeutic challenge. Patients with MD range from minimally symptomatic, highly functional individuals to severely affected, disabled patients. Current management strategies are aimed at controlling the acute and recurrent vestibulopathy but offer minimal remedy for the progressive cochlear dysfunction. In fact, recent research highlights the role of neurotoxicity in the pathogenesis of the progressive and residual cochleovestibular deterioration.
In this review, we provide a stepwise discussion of a patient with MD, focusing on disease progression, diagnosis, and treatment. Our goal is to provide the reader with a comprehensive discussion that helps guide management of this complex disease.
Keywords
Cochlear hydrops, Electrocochleography, Endolymphatic hydrops, Labyrinthectomy, Meniere’s disease, Vertigo, Vestibular-evoked myogenic potentials, Vestibular nerve section
A.S. was a 34-year-old healthy female, without significant past medical history, who presented to the otology clinic 10 years ago for evaluation of a 3-day complaint of a “blocked” right ear: muffled hearing, aural fullness, and a low-pitched “oceanlike” sound. She denied vertigo or significant disequilibrium. She denied any recent viral illnesses. The otoscopic examination was normal. She had a similar episode 8 months earlier that spontaneously resolved. She denied a history of migraine, photophobia, phonophobia, or visual aura associated with her hearing changes. An audiogram performed 10 years ago during the first event is shown in Fig. 13.1A , which demonstrated right-sided low-frequency sensorineural hearing loss (SNHL) rising to normal with an excellent word discrimination score (WDS). Her tympanogram and stapedial reflexes (not shown) were normal. A follow-up audiogram, performed 3 weeks following the initial presentation ( Fig. 13.1B ), showed normal hearing thresholds bilaterally.
An audiogram performed during our next clinic visit ( Fig. 13.1C ) revealed moderate rising to mild low-frequency SNHL for the right ear with a WDS of 84%. The Stenger test was negative.
Additional testing was performed to aid in diagnosis. A gadolinium-enhanced magnetic resonance imaging (gadolinium-MRI) centered on the internal auditory canals was normal. Electrocochleography (ECoG) showed an elevated summating potential/action potential ( SP/AP) ratio of 0.64/0.74 on the right side ( Fig. 13.2 ), with the contralateral ear showing a normal ratio (<0.4—not shown). The presumed diagnosis was cochlear hydrops (CH). She completed a 10-day course of prednisone, and instructions were given for a low-salt diet. Her hearing returned to normal.
Six months later the patient developed a recurrence of her right-sided hearing loss, aural fullness, roaring right-sided tinnitus, and a vertigo spell that lasted approximately 3 hours and was associated with nausea and vomiting. She also described a sensation of falling backward. On examination, she had right-beating horizontal nystagmus with a slight torsional component, increasing in amplitude on right lateral gaze. The audiogram showed moderate rising to mild SNHL in the right ear ( Fig. 13.1D ) , with a WDS of 76%. A vestibular-evoked myogenic potential (VEMP) showed an increased threshold on the right side ( Fig. 13.3 ) . She was treated with a course of steroids and started on hydrochlorothiazide and triamterene. The patient’s symptoms were consistent with the diagnosis of right-sided probable Meniere’s disease.
Introduction
Meniere’s disease (MD) is characterized by episodic vertigo, fluctuating hearing loss, aural pressure, and tinnitus, usually in one ear. Since its description by Prosper Meniere in the Gazette médicale de Paris in 1861, the pathophysiology and management of MD has been a controversial topic. Depending on the geographic location, the incidence of MD varies between 4.3 and 15.3 per 100,000. Affected individuals are usually between the third and seventh decades of life with a female to male ratio of 1.3:1.
There have been several classification schemes to define MD. Most recently, the Barany Society, in conjunction with numerous other international groups, including the American Academy of Otolaryngology–Head and Neck Surgery, proposed a simplified classification scheme ( Table 13.1 ). This scheme identifies two groups: definite and probable MD. Alternatively, staging systems have been proposed that are based on the residual hearing and residual vertigo after treatment ( Tables 13.2 and 13.3 ). These staging systems may be used to assess the degree of disability and help quantify treatment efficacy. Furthermore, the staging systems allow for uniform reporting of outcomes for various treatment modalities.
| Definition | Symptoms |
|---|---|
| Definite Meniere’s disease |
|
| Probable Meniere’s disease |
|
| Stage | Four-Tone Average (dB) |
|---|---|
| 1 | ≤25 |
| 2 | 26–40 |
| 3 | 41–70 |
| 4 | >70 |
| Numerical Value | Class |
|---|---|
| 0 | A |
| 1–40 | B |
| 41–80 | C |
| 81–120 | D |
| >120 | E |
| Secondary treatment initiated due to disability from vertigo | F |
The diagnosis of MD, an idiopathic condition, is made after excluding other causes that may mimic the disorder. These conditions can be infectious (e.g., otosyphilis), neurologic (e.g., migraine), autoimmune (e.g., Cogan’s syndrome, autoimmune inner ear disease), and neoplastic (e.g., intralabyrinthine or vestibular schwannomas, endolymphatic sac [ELS] tumors) ( Table 13.4 ).
| Neoplastic | Vestibular schwannoma |
| Endolymphatic sac tumor | |
| Meningioma | |
| Genetic | Autosomal dominant sensorineural hearing loss type 9 (DFNA9) caused by COCH gene |
| Autosomal dominant sensorineural hearing loss type 6/14 (DFNA6/14) caused by WSF1 gene | |
| Autoimmune | Cogan’s syndrome |
| Autoimmune inner ear disease | |
| Susac’s syndrome | |
| Vogt-Koyanagi-Harada syndrome | |
| Infectious | Otosyphilis |
| Neuroborreliosis | |
| Neurologic | Vestibular migraine |
| Cerebrovascular events/transient ischemic attack/stroke | |
| Vestibular paroxysmia (neurovascular compression syndrome) | |
| Anatomic | Third window syndromes including superior canal dehiscence, enlarged vestibular aqueduct, perilymphatic fistula |
In this chapter, we present a clinical vignette of a patient with MD who ultimately displays the full spectrum of the disease, and we discuss the clinical presentation, the diagnostic evaluation, and the different therapeutic modalities available to patients with this challenging disease.
What Are the Diagnostic Criteria for Meniere’s Disease?
The current consensus guidelines published in 2015 by the Barany Society after collaboration with an international group of experts identify two diagnostic categories for MD summarized as follows: definite and probable MD. The criteria for definite MD are “(1) two or more spontaneous episodes of vertigo each lasting 20 minutes to 12 hours; (2) audiometrically documented low- to medium-frequency SNHL in the affected ear on at least one occasion before, during, or after one of the episodes of vertigo; (3) fluctuating aural symptoms including hearing, tinnitus, or aural fullness in the affected ear; and (4) not better accounted for by another vestibular diagnosis.” According to these criteria, there may be nonsimultaneous onset of vertigo and hearing loss. In some patients, the hearing loss may precede the onset of vertigo by several months or years. Alternatively, episodic vertigo may precede the onset of hearing loss by weeks to months, although vestibular symptoms are usually accompanied by tinnitus and aural fullness. Some patients experience an increase in tinnitus intensity or aural fullness associated with the episodes of vertigo.
Probable MD is noted to include one or two episodes of vertigo or dizziness lasting 20 minutes to 24 hours. Patients can also experience fluctuating aural symptoms including hearing loss, tinnitus, and aural fullness in the affected ear. Patients with probable MD do not have documented low-frequency hearing loss or do not describe true vertigo symptoms.
Differential Diagnosis of Meniere’s Disease—Migraine and Meniere’s Disease
The diagnosis of MD is one of exclusion. The practitioner must confirm that no other etiology is the likely cause of symptoms. Approximately 1% of the population suffers from vestibular migraine (see Chapter 11 ). Early in the course of MD, before the patient manifests all symptoms of the disease, MD may be very difficult to be distinguished from vestibular migraine, as these disorders share many similar symptoms. Although patients with vestibular migraine may have fluctuating hearing, tinnitus, and aural fullness with each episode, the hearing loss usually does not progress to the levels seen in MD. Furthermore, many migraine patients report that vestibular symptoms can last up to 72 hours, which is highly unusual in MD. Some patients may manifest symptoms consistent with both disorders. Diagnosis of migraine is more common in patients with a definitive diagnosis of MD.
What Is the Role of Adjunctive Tests in the Diagnosis of Meniere’s Disease?
A national survey showed that depending on the region (West, Midwest, Northeast, New England, and Atlantic coast), 26.9%–46.7% of treating otolaryngologists relied on history, physical examination, and audiometry only to establish the diagnosis of MD. Others obtained adjunctive tests to support their diagnosis.
Electrophysiologic studies
In recent years, several diagnostic tests have been proposed to study the presence of endolymphatic hydrops (ELH) and complement the diagnosis of CH or MD. Two electrophysiologic tests merit mention: ECoG and cervical and ocular vestibular-evoked myogenic potentials (cVEMP and oVEMP).
ECoG is recorded in response to condensation and rarefaction click or tone-burst stimuli. The SP and AP of the eighth nerve are recorded via ear canal or transtympanic electrodes. An elevated SP/AP ratio (>0.4) and/or a widened AP width (>3 ms) are considered to be indicative of ELH. The alteration of SP and AP morphology in the hydropic ear is thought to result from a mechanical asymmetry in the basilar membrane (i.e., nonlinear basilar membrane vibration). Reports in the literature regarding sensitivity and specificity of ECoG vary widely. Ge X et al. reviewed 1549 patients with MD and found an elevated SP/AP ratio in 71.6%. They also showed that the sensitivity of ECoG increased with duration and severity of the disease. The sensitivity increases from 71% in stage 1 disease to 90% in stage 4 disease and from 43% in MD of less than 1 year duration to 100% when MD has been present for over 30 years. Others have reported combining the SP amplitude, SP area, SP/AP area ratio, and total SP/AP area to improve diagnostic accuracy. Abnormal ECoG findings for MD will be present when the disease is active; if the disease is not active, ECoG results may be normal; therefore, a negative ECoG study does not rule out MD (false negative).
The cVEMP is a short latency (8 ms) inhibitory potential of the ipsilateral sternocleidomastoid muscle evoked by brief and loud (>85 dB) click or tone-burst stimuli. The cVEMP is thought to be a recording of vestibulocollic reflex activity generated in the saccule and carried via the inferior vestibular nerve. Results of cVEMP testing in patients with MD are somewhat contradictory. MD patients may have elevated or absent VEMP thresholds compared with controls. These findings are more common in MD patients with Tumarkin’s crisis and are seen in 27% of the contralateral asymptomatic ears of affected individuals. Other studies have shown no difference between MD patients and control patients with regard to either VEMP amplitude or threshold. The sensitivity of cVEMP for a diagnosis of MD ranges from 50% to 63%. However, the cVEMP peak to peak amplitude may be a useful measure to monitor the progression of MD, as this value decreases over time.
The oVEMP reflex arc involves the contralateral orbicularis oculi and may be mediated partially by the utricle. oVEMPs are less frequently abnormal in patients with MD, particularly in early stages of the disease. Chen et al. found that only 16% of subjects had abnormal oVEMP responses, and the majority of these abnormalities were seen in patients with long-standing MD.
We feel that both cVEMP and ECoG can be used to complement the clinical picture but should not be the sole basis for or against diagnosis.
Caloric testing and head thrust testing
The role of videonystagmography (VNG) in the diagnosis of MD is somewhat limited. Significant caloric weakness is present in 42%–73% of patients with MD. Complete loss of function is seen in 6%–11%. Approximately 23%–29% of patients will have an abnormal angular vestibulo-ocular reflex on head thrust testing with gain asymmetry and phase lead being the most common findings.
We feel that caloric testing is useful in the (1) assessment of contralateral function before an ablative procedure, (2) assessment of residual function after an ablative procedure, and (3) assessment of ipsilateral function—if residual function is good, we favor a nondestructive procedure.
Retrocochlear studies
When surveyed for workup of retrocochlear pathology, 57.7%–93.3% of otologists obtained retrocochlear studies. One of the diagnostic criteria of MD is that other causes have been ruled out; therefore, we obtain a gadolinium-enhanced MRI of the internal auditory canals on all of our MD patients.
What Is Cochlear Hydrops? What Is Its Significance?
The term “cochlear hydrops” has been used to describe fluctuating hearing loss without associated vertigo. This may represent an earlier phase of a continuum ranging from mild cochlear involvement to full cochleovestibular dysfunction seen in MD.
House et al. studied the relationship of CH and MD. In their retrospective review of 950 “hydropic” ears, 71% were diagnosed with unilateral MD and 29% were labeled as unilateral CH. Bilateral MD (BMD) at presentation was seen in 11% with another 14% of unilateral MD becoming BMD. Of patients initially diagnosed as having unilateral CH, 33% developed MD over an average of 7.6 years of follow-up.
What Is the Pathophysiology of Cochlear Hydrops and Meniere’s Disease?
Although ELH is felt to be the underlying histopathologic finding in MD, to date no histopathologic study has confirmed the presence of ELH in patients with CH. Despite the lack of direct evidence of this association, electrophysiologic studies demonstrating elevated SP/AP ratio suggest ELH.
The pathophysiology of hydrops remains unknown. Several intrinsic (genetic, anatomical, autoimmune, or vascular) and extrinsic (allergy, viral, neoplastic, or trauma) causes can result in the disturbance of mechanisms involved in the regulation of endolymphatic fluid homeostasis.
Work to identify an underlying pathophysiology of ELH has identified several possible gene products for the disorder. Abnormal distribution of aquaporin 4 and 6, transmembrane water channels, may be the underlying cause of the ELH seen in MD patients. Genetic polymorphisms have been identified in these genes in MD patients. Other histochemical abnormalities noted in MD patients include abnormally thickened basement membranes and loss of the neuroepithelium in the saccule and semicircular canals. Whether this disturbance causes a predominant alteration in the longitudinal versus radial flow of the endolymph has been long debated. On the other hand, it remains unclear whether the subsequent hydrops is the result of a cytochemical abnormality or an anatomical anomaly.
In fact, the relationship of ELH to the symptoms of MD has also been questioned, raising debate as to whether the observed ELH is the direct pathologic initiator of cochleovestibular dysfunction or “epiphenomena” of subtler biochemical perturbations. In a review of their temporal bone registry, Merchant et al. found that all 28 patients with Meniere syndrome had evidence of ELH. However, of the 79 patients with ELH only 51 had Meniere’s symptoms. Classic symptoms were absent in 9 of the 35 patients with “idiopathic hydrops” and in 42 of the 44 patients with “secondary hydrops.”
In an effort to identify ELH with more certainty in vivo, Nakishima et al. described visualization of ELH in MD patients using intratympanic gadolinium and delayed high-resolution (3T) MRI; however, intratympanic gadolinium administration is off-label; therefore an intravenous (IV) gadolinium protocol has been developed. This MRI technique has subsequently shown higher rates of ELH in patients with MD compared with control patients, with sensitivity for diagnosis of 85%, and has significant promise in diagnosing hydrops and confirming the diagnosis of MD.
During the following year, our patient had a total of five episodes of severe vertigo associated with aural fullness, fluctuating hearing, and tinnitus. Over the course of that year, she developed a progression of her hearing loss. The audiogram showed moderate low-frequency SNHL in the right ear, with a WDS of 72% ( Fig. 13.1E ) . Three of the spells responded to a steroid taper and a regimen of antiemetics. Two episodes were treated with intratympanic injections of dexamethasone (IT-Dex) that gave temporary relief of vertigo. Her hearing remained unchanged, and she acquired a hearing aid for hearing assistance.
Nine months later, she developed a recurrence of vertigo spells occurring weekly. These spells did not respond to a combination of oral and intratympanic steroids. A Meniett (Norcross, GA) device was used without success. Her audiogram was unchanged, and she continued to use her hearing aid.
At that time, destructive and nondestructive options were discussed owing to the weekly vertigo spells. She underwent ELS decompression with placement of a shunt (endolymphatic sac surgery [ESS]). The sigmoid was noted to be far-forward requiring decompression. The sac was hypoplastic and inferiorly displaced. This resulted in the complete resolution of her vertigo spells. Her hearing remained stable. Nevertheless, she continued to complain of moderate to severe roaring tinnitus and a constant sensation of aural fullness.
What Is the Role of Medical Management?
The medical management of MD includes a low-salt diet, avoidance of caffeine derivatives and alcohol, diuretics, vasodilators, and steroids.
Diuretics and low-sodium diet are effective in controlling the symptoms of MD in 71%–79% and is the preferred first-line therapy for patients with MD. Initially described in the 1930s by Furstenburg et al., the low-sodium diet with diuretics (800–1000 mg/day and ammonium chloride) has evolved over time to a slightly more liberal sodium allowance (1500–2000 mg/day) and use of a potassium-sparing diuretic (hydrochlorothiazide with triamterene). A Cochrane database review of all prospective randomized control trials (RCTs) between 1966 and 2005, comparing diuretics to placebo, failed to show a single trial of good enough quality to meet the standard criteria set for review.
Another Cochrane database review of all RCTs comparing betahistine (a vasodilator) to placebo between 1966 and 1999 was completed. The analysis of six trials with 162 patients of good enough quality to meet the inclusion criteria failed to show any benefit of the betahistine. A recently conducted RCT of betahistine versus placebo failed to find significant benefit of either a low or high dose of betahistine in terms of vertigo control when compared with placebo.
Steroids, whether administered orally or intratympanically, have been used to treat acute exacerbations of MD. In a series of 129 patients with unilateral MD, Boleas-Aguirre et al. demonstrated that dexamethasone (12 mg/mL) administered intratympanically resulted in vertigo control in 91% of patients. Although more than half the patients responded to one or two injections, 21% required more than four injections. A meta-analysis by the Cochrane review identified significant improvement in vertigo episodes over a 24-month follow-up period with intratympanic dexamethasone (4 mg/mL) treated once daily for 5 days when compared with placebo.
In a recent survey of general otolaryngologists and neurotologists, several differences in medical management were identified between the groups. Neurotologists were more likely to prescribe a low-salt diet and use intratympanic medications than their general otolaryngology counterparts, while both physician groups used diuretic therapy equally.
What Is the Role of Vestibular Rehabilitation in the Acute Phase?
The role of vestibular rehabilitation in the acute phase of the disease has been questioned. Because of the fluctuating and dynamic nature of the vestibular symptoms seen in MD, most physicians feel that vestibular rehabilitation has limited benefits. Although the acute vertiginous spells are usually self-limited, chronic unsteadiness between the episodes of vertigo is a common complaint in patients with MD. Gottshall et al. showed that vestibular rehabilitation, even outside the acute care of patients with surgically ablated vestibular function, seems to improve the overall balance function in both patient-reported and objective measures (see Chapter 19 ).
What Is the Initial Treatment if Medical Therapy Fails?
In a survey by Kim et al., 50% of otologists proceed with ESS, whereas 39% will perform an intratympanic injection of gentamicin (IT-Gent). The rest will offer a Meniett (9%) or a vestibular nerve section (VNS) (2%). However, positive pressure therapy, such as the Meniett device, has not been shown via meta-analysis to significantly impact vertigo spells.
Controversies with endolymphatic sac surgery
A detailed review of this topic is beyond the scope of this chapter. The reader is referred to several more comprehensive reviews of the subject, including Sood et al. and Lim et al. However, we will highlight some of the pertinent clinical studies.
Whether limited to sac decompression and/or placement of a shunt, the efficacy of sac surgery has been and continues to be debated. The decompression of a tight ELS, the alteration of the neovascularization in the perisaccular region, the passive diffusion of endolymph, the creation of an osmotic gradient, and the decreased production of endolymph have all been proposed as potential mechanisms of action.
Is endolymphatic sac surgery better than natural history?
Many authors questioned the efficacy of this procedure when compared with natural history (NH). Others have questioned its long-term efficacy.
Quaranta et al. retrospectively evaluated 38 patients with intractable MD with a minimum of 7 years follow-up. Twenty patients underwent ESS and eighteen were offered surgery but declined (NH group). In their sample, 85% of the patients in the ESS group and 74% of the NH patients had complete or substantial control of vertigo. The difference between the two groups was not significant initially; however, it was significant at 2 and 4 years follow-up. At 2 years, 65% of ESS patients had complete or substantial control of vertigo, and at 4 and 6 years 85% of patients reported satisfactory relief. Only 32% of the NH patients had complete or substantial control of vertigo at 2 years. This percentage rose to 50% at 4 years and to 74% at 6 years. Hearing results between the two groups were not significantly different.
Silverstein et al. performed a retrospective study comparing patients who were offered surgery but declined (N = 50) with those who underwent surgery (N = 83). Of the nonoperated group, 57% had complete control of vertigo at 2 years; 71% had complete control after an average of 8.3 years. In the surgical ESS group, 40% had complete control of vertigo after 2 years; 70% had complete control after an average of 8.7 years. Their results suggest that ESS does not alter the long-term natural course of vertigo control in MD.
On the other hand, Telischi et al. reviewed the long-term vertigo control in 234 patients who underwent ESS followed for at least 10 years (mean, 13.5 years). Among these 234 patients, 63% did not undergo any further surgery to control vertigo, and an additional 17% required only revisions of the ELS shunt. Thus, 80% never required a destructive procedure. Of the 147 patients with only the original ESS, 93% reported no dizziness or mild to no disability. Of the group who underwent only revisions of the original shunt, 96% stated that they had no more dizziness or mild to no disability. In addition, Wick et al. described a cohort of ESS patients who received steroids intraoperatively using two different delivery methods: intratympanic only and intratympanic plus intra-ELS perfusion. Of the patients who had intratympanic steroids before postauricular incision, 83% achieved class A/B vertigo control with a mean follow-up of 95 months. Among the patients in the group who received intratympanic steroids plus intra-ELS steroid perfusion, 93% achieved class A/B vertigo control with a mean follow-up of 41 months. In contrast, 66% of patients in a control group who had shunting alone (i.e., no steroids) achieved class A and B control. Kato et al., using a disease-specific quality of life questionnaire, found that quality of life was improved in 87% of 159 patients with MD who underwent ESS.
Is endolymphatic sac decompression without shunt placement effective?
In a review of 94 patients with definite MD who underwent an ELS-mastoid shunt (54 patients) and ELS decompression (40 patients), Brinson et al. showed a class A or B vertigo control in 67% of the endolymphatic mastoid-shunt group and in 66% of the ELS decompression at 18–24 months follow-up. In a histologic study, Chung et al. demonstrated that some patients (53%) obtained relief from vertigo after putative ESS without either having the sac exposed or having a shunt placed within the lumen.
Regardless of the nuances in analyzing the outcome of ESS, the operation remains a commonly performed, nondestructive procedure.
After 2 years, our patient had a recurrence of her vertigo spells associated with a frequent sensation of disequilibrium. The disequilibrium is described as a sensation of being off-balance and unsteady, which seems to be exacerbated by sudden quick motions. This was accompanied by a constant foggy sensation in her head.
She felt quite disabled by her recurrent symptoms and decided to quit her job and stopped driving. A repeat audiogram was unchanged ( Fig. 13.1E ) . A VNG showed reduced caloric vestibular response of 81% for the right ear and findings consistent with right peripheral vestibular hypofunction ( Fig. 13.4 ) . She was counseled regarding chemical or surgical labyrinthectomy versus VNS. Because she felt that her hearing was serviceable, she elected to have a retrosigmoid selective VNS. Her hearing was preserved and she was able to continue using her hearing aid. Even though the overall frequency of vertigo spells improved, she continued to have attacks 12 months after surgery. She noted that her episodes had changed in character, and she described what seemed like an impending sensation of falling backward; she has had two episodes of Tumarkin’s crisis. A repeat VNG showed no response to standard caloric stimulation for the right ear. Ice caloric testing showed a residual response on the right side ( Fig. 13.5 ) . Her hearing deteriorated to severe SNHL ( Fig. 13.1F ) , and the WDS dropped to 24%. A VEMP showed absent responses ( Fig. 13.6 ) . She then elected to have IT-Gent using the titration method. This too failed to completely control her vertigo, and she then had a transmastoid labyrinthectomy (TML) that resulted in the resolution of the vertigo spells. She completed 4 months of vestibular rehabilitation.
