Peripheral Vestibular Disorders
Yuri Agrawal
Lloyd B. Minor
John P. Carey
GENERAL PRINCIPLES
The vestibular end organ consists of five organs: three semicircular canals (anterior, posterior, and horizontal), and two otolith end organs—the saccule and the utricle. The semicircular canals detect angular head rotation, while the otolith end organs detect translational head motion and the head’s orientation with respect to gravity. Hair cells in the right and left vestibular organs fire at a tonic baseline rate; if the head is turned toward the right, the hair cells of the right horizontal canal increase their firing rate while the hair cells of the left horizontal canal decrease their firing rate. The opposite changes occur with head turns to the left. Sensory input from the vestibular periphery is relayed centrally via the vestibular nerves; the superior vestibular nerve carries information from the horizontal and superior semicircular canals and the utricle while the inferior vestibular nerve transmits input from the posterior semicircular canal and saccule. The brain compares the inputs from right and left vestibular organs in order to determine that a change in head position has occurred and generates compensatory eye movements and postural changes. Collectively, the vestibular apparatus encodes information about head position and contributes to the maintenance of gaze and postural stability (via the vestibuloocular reflex (VOR) and vestibulospinal reflex respectively) (1).
In this chapter, we review peripheral vestibular disorders, which are characterized by pathology located in the peripheral vestibular end organs. The hallmark symptom of peripheral vestibular dysfunction is vertigo, which occurs if the right- and left-sided vestibular nerves fire asymmetrically in the absence of a head movement, creating an illusory sense of motion. We categorize peripheral vestibular disorders based on the clinical manifestations of vertigo (Table 166.1). Vertigo can be episodic, resulting from a reversible unilateral loss or gain of vestibular function, either of which can produce an asymmetry in the firing rates of the right- and left-sided vestibular nerves. Peripheral vestibular diseases characterized by episodic disruption of vestibular function include Ménière’s disease, where loss of vestibular function occurs for minutes to hours, as well as vestibular neuritis, labyrinthitis, and immune-mediated inner ear disease (IMIED), where loss of function can occur for over 24 hours. In migrainous vertigo, disruption of vestibular function may last for variable periods of time, in some events for minutes to hours, but in others for days. Peripheral vestibular disorders resulting from intermittent excitation in vestibular function include benign paroxysmal positional vertigo (BPPV) and superior canal dehiscence (SCD) syndrome. Perilymph fistulas may produce either an episodic disruption or excitation of vestibular function. A third category of peripheral vestibular disorders are those that result from chronically inadequate vestibular function. Chronic unilateral loss of vestibular function can be due to incomplete recovery after vestibular neuritis or labyrinthitis, long-term sequelae of Ménière’s disease, damage from cholesteatoma or chronic otitis media, etc. Some specific other causes are discussed in other chapters, including temporal bone trauma (Chapter 150) or acoustic neuroma (Chapter 159). Chronic bilateral vestibular dysfunction typically occurs in the setting of a systemic exposure, such as to aminoglycoside antibiotics or chemotherapeutic agents, or may be genetic in origin.
BRIEF EPISODIC DISRUPTION OF UNILATERAL VESTIBULAR FUNCTION
Ménière’s Disease
Ménière’s syndrome is an inner ear disorder characterized by spontaneous attacks of vertigo, fluctuating low-frequency sensorineural hearing loss, aural fullness, and tinnitus. When the syndrome is idiopathic and cannot be attributed to any other cause (e.g., syphilis, IMIED, surgical trauma),
it is referred to as Ménière’s disease (2). Ménière’s syndrome exhibits a relapsing-remitting pattern, with episodic attacks terminated by periods of restitution to normal auditory and vestibular function. Additionally, auditory and vestibular function may decline over time (3).
it is referred to as Ménière’s disease (2). Ménière’s syndrome exhibits a relapsing-remitting pattern, with episodic attacks terminated by periods of restitution to normal auditory and vestibular function. Additionally, auditory and vestibular function may decline over time (3).
TABLE 166.1 BASIC PRESENTATIONS OF PERIPHERAL VESTIBULAR DYSFUNCTION | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Clinical Features
The prevalence of Ménière’s disease has been reported to range from 34.5 per 100,000 persons in Japan (4), 157 per 100,000 persons in the United Kingdom (5), 190 per 100,000 in the United States (6), to 513 per 100,000 in Finland (7). Disease onset typically occurs in the fourth to sixth decade of life, with a 1.3-1.9:1 female predominance (4, 6). The extent to which Ménière’s disease occurs bilaterally has been a subject of considerable controversy. House et al. (8) found a 24% overall prevalence of bilateral Ménière’s disease, with 11% being bilateral at initial presentation, and a 14% rate of progression from unilateral to bilateral disease. The diagnosis of Ménière’s disease is largely clinical at this time; there are no pathognomonic tests that confirm this diagnosis. The most widely-used guidelines to establish a diagnosis of Ménière’s disease were published by the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS), which termed “definite” Ménière’s disease as two or more spontaneous episodes of vertigo, each lasting 20 minutes or longer; hearing loss documented by audiograms on at least one occasion; tinnitus or aural fullness in the affected ear; and other causes excluded (typically with gadolinium-enhanced magnetic resonance imaging [MRI] of the cranial base) (9). The staging system established by the AAO-HNS is based on audiometric criteria, with 4-frequency pure-tone averages at 0.5, 1, 2, and 3 kHz of less than 25, 26 to 40, 41 to 70 and greater than 70 corresponding to Stages 1, 2, 3, and 4 respectively.
The presentation of Ménière’s disease typically includes recurring attacks of vertigo (96.2%), with tinnitus (91.1%) and ipsilateral hearing loss (87.7%) (10). The clinical course of Ménière’s disease varies considerably between patients, from long periods of remission punctuated by episodic attacks to intervals of unrelenting attacks. Longitudinal studies suggest that vertigo ceases spontaneously in 57% of cases at 2 years and 71% after 8.3 years (11). Patients classically present with a low-frequency sensorineural hearing loss that is fluctuating and progressive. With long-standing disease (greater than 10 years), the audiometric pattern flattens and the hearing loss typically stabilizes at a pure-tone average of 50 dB and a speech discrimination score of 50% (12). Profound sensorineural hearing loss occurs in 1% to 2% of patients (13); if the losses are bilateral, patients may benefit from cochlear implantation (14).
Endolymphatic Hydrops
Endolymphatic hydrops has long been held to be the pathologic basis for Ménière’s disease (15, 16, 17). Endolymph, the potassium-enriched fluid in the inner ear, may be either excessively synthesized or inadequately resorbed, resulting in expansion of the endolymphatic space (17, 18). Endolymphatic hydrops typically involves the pars inferior of the labyrinth (composed of the saccule and cochlea) (16, 19). The pars superior (utricle and semicircular canals) may also be involved in endolymphatic hydrops, although changes tend to be less dramatic and occur less frequently.
Several mechanisms have been suggested to explain how endolymphatic hydrops may produce the spontaneous attacks of vertigo characteristic of Ménière’s disease. The most prominent theory holds that hydropic distension of the endolymphatic duct causes rupture of the distended membranes, a phenomenon that has been observed throughout the labyrinth (20). Membrane rupture allows the potassium-rich endolymph to leak into the perilymphatic space and contact the basal surfaces of the hair cells as well as the eighth cranial nerve. Initial excitation and then subsequent inhibition of the hair cells manifests as a direction-changing nystagmus and may underlie episodic vertigo. Long-term declines in auditory and vestibular function may be the result of repeated exposure of the vestibular hair cells to toxic levels of potassium-enriched perilymph (21). Recent studies have challenged the primacy of endolymphatic hydrops in the pathophysiology of Ménière’s disease, and have suggested that endolymphatic hydrops may be a marker of disordered cochlear homeostasis but not necessarily directly responsible for the symptoms of Ménière’s disease (22).
Physiologic Tests in Ménière’s Disease
The use of electrocochleography is based on endolymphatic hydrops as a presumed pathologic correlate of Ménière’s disease. Electrical potentials generated by the cochlea are measured in response to repeated sound stimulation with clicks or tonebursts. The cochlear field potential responses include the cochlear microphonic potential and the summating potential (SP), both of which represent cochlear hair cell function, and the compound action potential (AP), which reflects auditory nerve activity and corresponds to wave I of the auditory brainstem reflex. The SP has been observed to be larger in response to clicks or more negative in response to tonebursts in patients with Ménière’s disease. Using clicks, for example, a typical upper limit of normal for the SP/AP ratio is 0.4 (23). SP changes in Ménière’s disease are thought to reflect hydropic distension of the basilar membrane into the scala tympani causing an increase in the normal asymmetry of its vibration. The sensitivity of the SP/AP ratio has been reported to be 50% to 70% (24), and efforts to augment the sensitivity have included combining the SP/AP ratio with SP amplitude, AP latency, and audiometric parameters (25). Yet while studies find that electrocochleographic findings with audiometric considerations can segregate cases of definite Ménière’s disease from normals, the ability of electrocochleography to discriminate between cases of possible or probable Ménière’s disease and normals is less clear (25). It is in these less-clear cases that additional information would be most helpful.
Caloric and head impulse testing are both tests of semicircular canal function. In caloric testing, bithermal irrigation is applied to the external auditory canals, which causes a convective movement of endolymph within the ipsilateral horizontal semicircular canal (26). The movement of fluid within the horizontal canal results in excitatory or inhibitory deflection of the cupula (depending upon the direction of endolymph flow). Motion of the cupula then leads to hair cell excitation or inhibition with a corresponding change in the discharge rate of vestibularnerve afferents. Compensatory eye movements are thereby elicited (corresponding to the slow phases of nystagmus), followed by fast resetting eye movements (corresponding to the fast phase of nystagmus). The maximum velocities of the slow phases of nystagmus are compared bilaterally and used to compute unilateral weakness or caloric asymmetry. Depending on the normative data developed by individual vestibular laboratories, a caloric asymmetry of 20% or greater is usually considered indicative of unilateral peripheral vestibular hypofunction.
Head impulse (or head thrust) testing assesses the integrity of the angular vestibuloocular reflex (AVOR). Head and eye movements are recorded during high-velocity, highacceleration rotary head impulses in the excitatory direction for each of the six semicircular canals. Normal subjects are able to maintain visual fixation on a target during rapid head movement and thus have gain values (computed as the ratio of eye velocity to head velocity) close to 1.0 (27).
A significant reduction in the caloric response of affected ears has been observed in 42% to 79% of individuals with unilateral Ménière’s disease (28, 29, 30, 31, 32, 33, 34). In contrast, abnormalities of the AVOR in Ménière’s disease are much less prevalent, although there appears to be a correlation between head impulse test gain asymmetry and caloric unilateral weakness percentage (29). Although caloric and head impulse testing are both measures of semicircular canal function, they may be capturing distinct phenomena. Caloric irrigation causes a slow convective flow of endolymph and provides a low frequency stimulus to the vestibular system. In contrast, high-velocity rotary head thrusts cause rapid endolymph movement and generate a high frequency input to vestibular afferents. It is possible that Ménière’s disease preferentially impairs the ability of the vestibular apparatus to process low-frequency signals. It should be noted that the low-frequency caloric stimulus is a nonphysiologic input, whereas the high-frequency head thrust approximates commonly occurring stimulus frequencies to the vestibular apparatus during walking and running. Thus it is also possible that mechanisms of central adaptation can only be established for physiologic stimuli (leading to normal responses to head impulse testing) but not for inputs outside the normal range (i.e., caloric stimuli).
Vestibular-evoked myogenic potentials (VEMPs) are thought to reflect otolith function. The cervical VEMP (cVEMP) in response to air-conducted clicks or tonebursts appears to be generated by a sacculocollic reflex. In the afferent limb of this reflex pathway, acoustically-sensitive cells in the saccule respond to brief, loud, monaural sound stimuli and transmit an electrical signal centrally via the inferior vestibular nerve. The efferent limb of this reflex arc sends an inhibitory impulse to the fibers of the ipsilateral sternocleidomastoid muscle; electromyographic recordings from this muscle in response to a sound input thus reflect saccular function (35, 36).
cVEMP responses to click stimuli were observed to be delayed or absent in 51% to 54% of patients with Ménière’s disease (37, 38) compared to the normal clickevoked response rates of 98%. Normal individuals demonstrate greatest sensitivity of their sacculocollic reflex over the 200 to 1,000 Hz frequency range (39, 40); patients with Ménière’s disease are noted to exhibit altered frequency tuning, such that the greatest sensitivity of the sacculocollic reflex appears to occur at higher frequencies and across a broader frequency range compared to normal subjects (41). Frequency tuning may be a function of the resonance properties of the saccule (which in part reflects the size of the saccule). Moreover, individuals with severe saccular dysfunction who experience drop attacks—otherwise known as otolithic crises of Tumarkin (42, 43)—have the greatest blunting and frequency shift of their cVEMP tuning curves (44). Additionally, 27% of individuals with unilateral Ménière’s disease were found to have cVEMP response abnormalities in their unaffected ear; the cVEMP tuning curves in these asymptomatic ears were noted to be
intermediate in phenotype between affected and normal ears (45). cVEMP testing shows particular promise as a measure of Ménière’s disease severity and in its ability to prognosticate bilateral disease.
intermediate in phenotype between affected and normal ears (45). cVEMP testing shows particular promise as a measure of Ménière’s disease severity and in its ability to prognosticate bilateral disease.
Treatment
Given that the pathologic basis of Ménière’s disease remains elusive, it follows that a curative treatment remains to be elucidated. Current therapies are directed at mitigating symptoms, particularly vertigo. First-line medical regimens include salt restriction and diuretics, aimed at alleviating endolymphatic hydrops. Betahistine, an H1-histamine receptor antagonist that increases inner ear blood flow, has been shown to reduce the frequency and severity of vertigo episodes. Betahistine is widely used in Europe in the treatment of Ménière’s disease although its use is limited in the United States given insufficient evidence for its efficacy (46). Increasing evidence supports the use of corticosteroids, particularly delivered intratympanically, in the treatment of Ménière’s disease. One large retrospective study found that control of vertigo symptoms was achieved in 91% of patients treated with intratympanic dexamethasone, allowing them to defer or avoid ablative therapies (47).
Medical therapy is insufficient to control vertigo symptoms in 10% of cases (48). Options for patients with refractory Ménière’s disease include surgical decompression of the endolymphatic system, and surgical or chemical ablation of vestibular function. In endolymphatic sac surgery, a transmastoid approach is used to decompress the sac with or without placement of a shunt to drain endolymph. Studies demonstrate positive outcomes from endolymphatic shunt surgery in terms of hearing preservation and vertigo control (49), although a recent metaanalysis found that there is insufficient evidence showing efficacy of this procedure relative to placebo (50). Selective vestibular neurectomy via middle fossa or posterior fossa approach has been shown to relieve vertigo symptoms in over 90% of cases, although potential complications of these procedures, including hearing loss, facial nerve weakness, cerebrospinal fluid (CSF) leak, speech and language deficits (from temporal lobe retraction in the middle fossa approach), and headaches (from the posterior fossa approach) must be considered. Surgical labyrinthectomy achieves excellent vertigo control rates, although hearing in the operated ear is abolished.
Surgical procedures are increasingly being supplanted by chemical ablation of the peripheral vestibular apparatus using intratympanic gentamicin. Gentamicin is a relatively selective vestibulotoxic aminoglycoside antibiotic that is preferentially taken up by type I hair cells of the vestibular neuroepithelium (51). The use of low-dose intratympanic gentamicin has been shown to yield 70% to 90% vertigo control rates (52), and is associated with hearing loss in only 17% of cases (53). We have demonstrated that AVOR gains in Ménière’s disease are typically normal before intratympanic gentamicin administration, and that they drop significantly after gentamicin, but not as much as after surgical labyrinthectomy (54). Studies in the chinchilla suggest that the lesion caused by intratympanic gentamicin primarily affects type I vestibular hair cells and may damage stereocilia on type II hair cells; however, vestibular nerve afferents continue to fire spontaneously after intratympanic gentamicin treatment (51, 55). These findings suggest that a benefit of intratympanic gentamicin treatment over surgical ablation is that the gentamicin lesion is partial and does not create the kind of large static imbalance in vestibular nerve firing that accompanies surgical ablation. Therefore, adaptation to the intratympanic gentamicin lesion may be less challenging than to surgical ablation.
Migrainous Vertigo
Clinical Features
Vertigo is a common symptom of migraines, occurring in 25% of migraine patients (56). Vertigo may occur as an aura, which is a focal neurologic symptom preceding the headache. More commonly, however, attacks of vertigo occur independently and in some cases in place of the headache (57). In fact, typical migraine headaches occur with the vertigo spells in only about half of cases (58, 59). Patients often report a prior history of migraine headaches that seem to have resolved. Milder head or neck pain or pressure may replace the pounding headaches and accompany the dizziness symptoms. The dizziness can be described as vertigo (spinning, rocking, swaying) or simply disequilibrium. The symptoms may be quite variable in duration, lasting minutes to days in episodic cases, or may present as constant disequilibrium lasting months. In approximately half of episodic cases the spells of vertigo or disequilibrium last more than a day (60), a feature that often helps distinguish migrainous vertigo from Ménière’s disease. Photophobia, menstrual association, and nasal stuffiness at the time of attack all increase the odds that vertigo is migrainous in origin, especially if there is no history of hearing fluctuation or positional component (61). A family history of migraines may be helpful in the diagnosis, as may a history of unexplained falling spells or motion sensitivity as a child (62). Interestingly, the prevalence of migraine in patients with Ménière’s disease is significantly higher than in the general population (63, 64), and there may be a pathophysiologic link between the two disorders. This makes it sometimes difficult to distinguish the two in a given patient, and both may need to be treated for successful control of vertigo in some individuals.
Pathophysiology
Two pathophysiologic mechanisms have been hypothesized to cause migraine-associated vertigo: central electrical disturbances and peripheral trigeminovascular dysfunction. Functional MRI studies have demonstrated the centrifugal spread of depressed metabolic activity originating from the occipital cortex during visual aura progression (65).
This cortical spreading depression appears to represent a propagating wave of disturbed membrane ionic homeostasis; indeed, studies have linked at least one form of migraine (familial hemiplegic migraine) to several possible mutations, for example, in a calcium ion channel gene on chromosome 19 (66). Baloh (67) has suggested that the features of more common migraine syndromes resemble those of many inherited ion channelopathies. This may account for the efficacy of agents that cause an ion channel blockade, such as calcium channel blockers or beta-blockers, in the prevention and treatment of migraine. The spreading depression triggered by ion channel defects appears to affect not only cortical structures but also more caudal regions in the brainstem (68). A variety of structures may be affected by aberrant electrical activity in the tightly-packed brainstem anatomy. Involvement of the medial lemniscus, through which touch and proprioceptive fibers ascend to the thalamus, may contribute to the pain and allodynia (hypersensitivity to touch) experienced by migraineurs. Involvement of the ascending fibers of the reticular activating system, which regulate alertness, may explain the fatigue that often occurs during and after a migraine episode. Spread of the metabolic depression to the descending fibers of the brainstem that are responsible for the common integrator function of the vestibular and oculomotor systems may lead to disturbances of the VOR. The electrical disturbance may also affect the cochlear and vestibular nuclear complexes, producing the symptoms of hearing loss and vertigo. Indeed, transient sensorineural hearing loss as well as reduction in vestibular responses have been documented in patients with migraine (57, 69, 70).
This cortical spreading depression appears to represent a propagating wave of disturbed membrane ionic homeostasis; indeed, studies have linked at least one form of migraine (familial hemiplegic migraine) to several possible mutations, for example, in a calcium ion channel gene on chromosome 19 (66). Baloh (67) has suggested that the features of more common migraine syndromes resemble those of many inherited ion channelopathies. This may account for the efficacy of agents that cause an ion channel blockade, such as calcium channel blockers or beta-blockers, in the prevention and treatment of migraine. The spreading depression triggered by ion channel defects appears to affect not only cortical structures but also more caudal regions in the brainstem (68). A variety of structures may be affected by aberrant electrical activity in the tightly-packed brainstem anatomy. Involvement of the medial lemniscus, through which touch and proprioceptive fibers ascend to the thalamus, may contribute to the pain and allodynia (hypersensitivity to touch) experienced by migraineurs. Involvement of the ascending fibers of the reticular activating system, which regulate alertness, may explain the fatigue that often occurs during and after a migraine episode. Spread of the metabolic depression to the descending fibers of the brainstem that are responsible for the common integrator function of the vestibular and oculomotor systems may lead to disturbances of the VOR. The electrical disturbance may also affect the cochlear and vestibular nuclear complexes, producing the symptoms of hearing loss and vertigo. Indeed, transient sensorineural hearing loss as well as reduction in vestibular responses have been documented in patients with migraine (57, 69, 70).
Another possible mechanism to explain the observed labyrinthine dysfunction is activity in the trigeminovascular efferent system. Dysfunction of the trigeminal brainstem nuclei (possibly owing to spreading depression) may lead to aberrant efferent signals in the trigeminal nerve. The trigeminal nerve arborizes extensively in the head and neck, with efferents also demonstrated in the inner ear (71). Release of vasoactive compounds such as calcitonin gene-related peptide and Substance P by the trigeminal nerve may cause plasma extravasation and produce a local aseptic inflammation (72). Plasma extravasation from the spiral modiolar artery has been demonstrated after stimulation of the trigeminal ganglion, so it seems possible that a migrainous mechanism could directly affect cochlear and peripheral vestibular function (73). If so, this might explain the difficulty in separating some cases of migrainous vertigo from apparent Ménière’s disease, as the peripheral effects of such trigeminovascular disturbances might mimic what we now think of as Ménière’s disease.
Treatment
The treatment of migrainous vertigo can be quite successful if approached in a stepwise fashion, beginning with dietary and lifestyle modifications, and proceeding if needed to recognized migraine prophylactic agents (60). Lifestyle changes should include regular sleep and exercise, and the identification and avoidance of migraine triggers. Stress, hormonal changes, weather and barometric pressure changes often incite migraine attacks. Common food triggers include byproducts of food aging and fermentation, such as red wine, aged cheese, yeast bread and yogurt, which contain high levels of tyramine. Foods that contain amines similar to our own neurotransmitters, such as caffeine, nitrates and other preservatives, chocolate, and various forms of glutamate including monosodium glutamate, have also been found to be migraine triggers and should be avoided. For symptoms that are constant and for which triggers cannot be identified or eliminated, the use of medications that raise the threshold above which migraines are triggered should be considered. Such prophylactic medications include calcium channel blockers, beta blockers, antidepressants such as nortriptyline or venlafaxine, and anticonvulsants including sodium valproate, gabapentin, and topiramate. Prophylactic medications should be selected based on the tolerability of their side effects in a given patient. Typically, benefits are seen after 6 to 8 weeks of therapy, and a realistic goal is to reduce symptom frequency and severity by 50% to 70%. For migraine attacks that persist despite lifestyle and dietary modifications and the use of prophylactic medications, migraine abortive medications such as the triptans can be considered. Abortive medications should not be used more than six to eight times per month, given their known rebound effects. Vestibular rehabilitation therapy has also been shown to significantly improve functional status in patients with migraine-associated vertigo (74, 75).
Perilymph Fistula
Fractures of the bone of the labyrinthine capsule separating the inner ear from the middle ear and mastoid or disruption of the bone or membranes in the area of the oval or round windows can lead to a perilymph fistula with consequent sensorineural hearing loss and episodic vertigo (76
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