Diagnosis, new classification and treatment
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Background: Recent research findings have improved the understanding of the diagnosis, pathophysiology, genetics, etiology, and treatment of peripheral, central, and functional vestibular vertigo syndromes.
Method: A literature search, with special attention to the current classification, treatment trials, Cochrane analyses, and other meta-analyses.
Results: There are internationally accepted diagnostic criteria for benign positional paroxysmal vertigo, Menière’s disease, bilateral vestibulopathy, vestibular paroxysmia, and functional dizziness. Whether an acute vestibular syndrome is central or peripheral can usually be determined rapidly on the basis of the history and the clinical examination. “Cerebellar vertigo” is a clinically important entity. For bilateral vestibulopathy, balance training is an effective treatment. For Menière’s disease, preventive treatment with betahistine (48 mg and 144 mg per day) is not superior to placebo. For vestibular paroxysmia, oxcarbazepine has been shown to be effective. Treatments that are probably effective for functional dizziness include vestibular rehabilitation, cognitive behavioral therapy, and serotonin reuptake inhibitors.
Conclusion: The diagnostic assessment of vestibular syndromes is much easier for clinicians now that it has been internationally standardized. There is still a lack of randomized, controlled trials on the treatment of, for example, Menière’s disease, vestibular migraine, and “cerebellar vertigo.”
Vertigo or dizziness is not a disease in itself, but rather a leading symptom of various diseases of differing etiologies. These include dysfunction of the vestibular system, both peripheral (inner ear, vestibular nerve) and central (brainstem, cerebellum); functional dizziness; and diseases of other causes, including blood pressure regulation disorders, such as orthostatic dizziness, and adverse drug effects. Vertigo is often wrongly attributed to an isolated polyneuropathy or to poor vision, as these conditions can also cause gait instability. Its incidence is approximately 11% per year; individuals with have a markedly higher mortality (adjusted for age, sex, and comorbidities) than those without vertigo or dizziness (adjusted odds ratio 1.7) (1). The lifetime prevalence of moderate to severe vertigo and dizziness is approximately 30% (e1, e2). The relative frequency of the individual diseases is shown in Figure 1.
After reading this article, the reader should:
- Have a new attitude to vertigo and dizziness: on the basis of the history and physical examination, even the non-specialist physician can now, in many cases, diagnose vertigo and dizziness rapidly and easily and apply effective treatment.
- Have better knowledge/skills in the following areas: internationally accepted diagnostic criteria, physical examination of the vestibular system, and treatment options, including physical therapy, drugs, psychotherapy, and, rarely, surgery.
Diagnosis and current classification
The diagnostic assessment of the various vestibular syndromes is based on the patient’s history and the clinical examination of the vestibular, ocular motor, and cerebellar systems. When the history is taken, the patient should be asked about the nature and temporal course of the symptoms. Did they begin suddenly? Are they continuous, or do they occur episodically? It should be determined which particular disorder is present: spinning vertigo, dizziness, postural imbalance, or light-headedness. The modulatory factors are also important, e.g., changes of body position or the activities the patient was engaged in when the symptoms arose. One should also ask about any accompanying symptoms and their localization. Is the inner ear, the brainstem, or the cerebellum affected? Or are the attacks typical of migraine? (Box).
In the physical examination, special attention should be paid to whether spontaneous or positionally induced nystagmus is present. Frenzel’s goggles and M glasses have proved to be simple, practical aids to nystagmus testing (Figure 2a) (2). The vestibulo-ocular reflex (VOR) should be evaluated with the head-impulse test (Figure 2b) and the diagnostic positional maneuvers (Figure 2c, d). Finally, stance and gait should be examined (Figure 2e, f). Basic, initial screening for hearing impairment can be performed with a tuning fork.
The two main ancillary laboratory tests for the function of the VOR are the video head-impulse test (e3) (eFigure), which is superior to clinical examination (3), and caloric testing of the horizontal semicircular canals. Finally, diagnostic assessment has been standardized and further simplified in the entirely clinically oriented, internationally accepted diagnostic criteria of the Bárány Society (free download: www.jvr-web.org/ICVD.html). Cochrane analyses and German clinical practice guidelines are listed in eTables 1 and 2.
We would like to emphasize that, contrary to widespread belief, the diagnosis of the more common vertigo syndromes is actually a simple (though by no means trivial) matter. A physician who is not a specialist in this area can usually make the right diagnosis. The new diagnostic criteria are particularly useful as a practical aid to the “closely listening and carefully examining clinician”. Consultation of a neurologist, otolaryngologist, or specialized center becomes necessary only if specialized ancillary testing is required, if the diagnosis is in doubt, or if the patient has not responded to a course of appropriate treatment.
Common vestibular syndromes of peripheral origin
Three types of peripheral vestibular disorders with typical signs and clinical symptoms can be differentiated on pathophysiological and functional grounds:
- Bilateral loss of function (partial or total) of the vestibular nerve and/or vestibular end organs: bilateral vestibulopathy;
- “Acute unilateral vestibulopathy” manifesting itself as an “acute peripheral vestibular syndrome”;
- Unilateral paroxysmal pathological excitation or, more rarely, inhibition of the vestibular nerve and/or vestibular end organs (BPPV, Menière’s disease, vestibular paroxysmia, third mobile window syndromes) (4).
In the following sections, the current methods of diagnostic assessment , pathophysiology, etiology, and treatment of the more common peripheral vestibular syndromes will be presented in the light of the above classification.
The diagnostic criteria for bilateral vestibulopathy are as follows (5):
- A chronic vestibular syndrome with at least two of the following symptoms: instability of stance or gait and/or motion-induced blurred vision or oscillopsia while walking or on rapid head movement and/or worsening of instability in the dark and/or on uneven ground.
- No symptoms while sitting or lying under static conditions.
- Bilaterally impaired or absent function of the horizontal vestibulo-ocular reflex (VOR), as documented by a bilaterally pathological video head-impulse test (vHIT) for the horizontal semicircular canal (VOR gain < 0.6) and/or bilaterally reduced caloric excitability (the sum of the peak slow phase velocity of the calorically induced nystagmus amounts to < 6°/s for each ear).
- Symptoms not better explained by another disease.
The diagnosis of bilateral vestibulopathy requires quantitative testing of vestibular function (5) (eFigure), as the bedside head-impulse test is of low sensitivity and specificity (3). In the absence of quantitative testing, only “probable bilateral vestibulopathy” can be diagnosed.
The various causes of bilateral vestibulopathy were analyzed in a retrospective series of 154 patients (6). Twenty different causes were found, identified with certainty in 47% of cases and considered only possible causes in another 22%; in the remaining 31%, the etiology remained unclear. Ototoxic drugs (in particular gentamicin), were most common, followed by genetic causes and bilateral Menière’s disease. Bilateral vestibulopathy can arise at any age. The average age at diagnosis lies between 50 and 60 years (for an overview, see ).
The four principles that guide treatment are as follows:
- Explaining the cause of the symptoms to the patient.
- Primary prevention, i.e., avoidance of ototoxic substances.
- Optimal treatment of the underlying disease, e.g., Menière’s disease.
- Physiotherapy (level I evidence) with daily balance training, particularly including head turning in all three planes, in order to train the vestibulo-ocular reflex (VOR training). Older patients, in particular, should additionally undergo training to prevent falls under the guidance of a physiotherapist (e4, 7, 8).
Acute unilateral vestibulopathy/vestibular neuritis
Acute unilateral vestibulopathy is characterized by spinning vertigo of acute onset that lasts for at least 24 h (9), accompanied by oscillopsia, a tendency to fall, and nausea. Furthermore, horizontal-torsional spontaneous nystagmus is seen, with the fast phase beating toward the presumably unaffected side; this can be suppressed by fixation. The head-impulse test demonstrates unilateral peripheral vestibular dysfunction of the vestibulo-ocular reflex (vHIT gain < 0.7) (eFigure) and/or a > 25% difference between the two sides on caloric testing. Moreover, the subjective visual vertical is pathologically tilted toward the side of the affected labyrinth.
No signs of a central ocular motor disturbance or acute hearing impairment are found.
This disease is also referred to as vestibular neuritis, neuronitis, or neuropathy.
In patients with clinical manifestations of an acute vestibular syndrome, the main differential diagnosis after acute unilateral vestibulopathy is a lesion of the brainstem or cerebellum (usually ischemic).
The probable, though not yet directly proven, etiology of acute unilateral vestibulopathy is reactivation of a latent herpes simplex virus 1 (HSV-1) infection. This hypothesis is supported, among other evidence, by a link to genetic variants of a host factor for HSV-1 replication that was revealed by a genome-wide association study (10).
The efficacy of steroids as an aid to the recovery of peripheral vestibular function in acute unilateral vestibulopathy has been shown in a randomized, controlled trial (11) but nonetheless remains controversial; at least one more randomized, controlled trial is needed. A prospective observational study indicated that the success of steroid treatment depends on the latency between symptom onset and the initiation of treatment (12). The efficacy of balance training in the treatment of acute unilateral vestibulopathy has been documented in multiple randomized trials. A particularly important component of balance training is rotation of the head with fixation of a visual target to enhance the central vestibular tonus imbalance, which is the adequate stimulus for initiating central vestibular compensation (e4, 8).
Benign paroxysmal positional vertigo
Recurrent attacks of spinning vertigo induced by changes in head position relative to the gravitational axis, lasting for several seconds each, are the main manifestation of benign paroxysmal positional vertigo. Nowadays videos of eye movements taken by the patient himself or herself, with the aid of screening techniques (smart devices [e5]) or with a smartphone (e6) can also be helpful to make the diagnosis.
Approximately 95% of all cases of benign paroxysmal positional vertigo are idiopathic. A multivariate analysis has shown that this condition is significantly associated with age, prior falls, and reduced physical activity (e7). Individuals with migraine are 2.5 times more likely to develop benign peripheral paroxysmal positional vertigo than others (e8).
The diagnostic criteria for benign paroxysmal positional vertigo of the posterior semicircular canal are as follows (13): The patient suffers from recurrent attacks of rotational vertigo induced by lying down supine or turning into supine position while lying down. Each attack lasts less than 1 min. Positional nystagmus is present, arising with a short latency after the lateral positioning maneuver (the diagnostic Sémont maneuver) (Figure 2) or the Dix–Hallpike maneuver. This nystagmus consists of a torsional component (the upper pole of the eyes beats toward the lower ear) combined with vertical upbeating nystagmus, and it typically lasts less than 1 min. Finally, the symptoms cannot be attributed to any other disorder.
The treatment of choice for benign paroxysmal positional vertigo of the posterior canal is the Sémont or Epley maneuver (level 1 evidence) (14). When these are correctly performed, the success rate is above 95%. Despite the efficacy of these repositioning maneuvers, older patients in particular tend to suffer much longer from the consequences of benign paroxysmal positional vertigo, with marked resulting impairment (e7, e9); follow-up appointments are therefore needed. Treating benign paroxysmal positional vertigo of the posterior canal with sedating antivertiginous drugs is not recommended for any more than a short time, and only if the patient suffers from marked nausea. There is no need to restrict the patient’s movements or positions during sleep (14).
Benign paroxysmal positional vertigo of the horizontal semicircular canal is much rarer. It causes linear, horizontal nystagmus (13).
The diagnostic criteria for Menière’s disease are as follows (15):
- Two or more spontaneous attacks of vertigo lasting 20 min to 12 h
- Audiometrically documented hearing loss for frequencies below 2000 Hz bone conduction (> 30 dB worse than the other ear in at least two neighboring frequencies), associated with vertigo attack
- Fluctuating tinnitus or fullness in the affected ear
- No evidence of another cause.
If low-frequency hearing loss has not been demonstrated audiometrically, then only the diagnosis of probable Menière’s disease can be made according to these criteria. It is very helpful that useful portable, iPad-based audiometric devices are now available with which patients can test their own hearing (e10).
The pathogenesis of Menière’s disease is thought to involve a multifactorial disequilibrium of inner-ear homeostasis (e11), with endolymphatic hydrops as the final common pathway. The latter can be seen on delayed contrast-enhanced magnetic resonance imaging (MRI) of the inner ear (Figure 3). The specificity of such findings for the diagnosis of Menière’s disease is a matter of controversy, because imaging studies reveal endolymphatic hydrops in the region of the saccule in 10% of normal persons and in 40% of patients with a sensorineural hearing loss of > 45 dB without vestibular symptoms (16).
Moreover, although nearly all patients with definite Menière’s disease have endolymphatic hydrops, the latter can also be seen in patients with vertigo syndromes of other etiologies, e.g., vestibular migraine (e12).
There is no consensus yet on the preventive treatment of Menière’s disease. The efficacy of individual treatments is hard to assess, because of the clinical heterogeneity of the disease, its fluctuating course, and its high rate of response to placebo (up to 70% ). At present, a stepwise concept is recommended, beginning with conservative treatment (e.g., betahistine), then non-destructive techniques (e.g., transtympanic cortisone application), and, finally, invasive destructive techniques (e.g., labyrinthectomy). There is no evidence to date for the efficacy of a low-salt diet, abstinence from coffee or alcohol, diuretic use, or endolymphatic sac surgery (8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, e13, e14).
Treatment with betahistine
Betahistine in a dose of 48 or 144 mg/d is not superior to placebo, according to a randomized, controlled trial on 221 patients in which a strong placebo effect was found (17).
Uncontrolled observational studies have shown that higher doses are associated with higher efficacy. Individual treatment trials suggest that combining orally administered betahistine with the MAO-B inhibitor selegiline may enhance its efficacy: this can be understood in light of the fact that 99% of orally ingested betahistine is metabolized in the gastrointestinal tract by MAO-B/A. This approach has received support from experimental studies in animals in a model of acute unilateral vestibulopathy (21). On the whole, more randomized and controlled trials are needed to study the therapeutic effects of betahistine.
Administration of gentamicin and steroids
The transtympanic administration of gentamicin reduces the frequency of the vertigo attacks (22). This is an ablative treatment that works by vestibulotoxic impairment of vestibular function. In approximately 20% of patients, there is ototoxic hearing loss. The utility of gentamicin is limited for this reason, and also because 45% of patients with Menière’s disease develop the condition bilaterally.
Transtympanic corticosteroid administration is an alternative treatment with demonstrated efficacy in double-blind, randomized, controlled trials (22). It is neither cochleotoxic nor vestibulotoxic.
If conservative treatment, including orally administered betahistine and transtympanic corticosteroids, is ineffective, surgery may be indicated (e13, e14). Endolymphatic sac surgery is recommended by many surgeons, but its efficacy has not yet been definitively demonstrated (20).
In advanced Menière’s disease, labyrinthectomy and simultaneous cochlear implantation leads to the cessation of the vertigo attacks and to an improvement of hearing.
This term, along with its clinical characteristics and pathophysiology, was introduced by Brandt and Dieterich in 1994 (23). The current diagnostic criteria for vestibular paroxysmia are as follows: At least ten attacks of spontaneous spinning or non-spinning vertigo; duration less than 1 min; stereotyped phenomenology in a particular patient; response to treatment with a sodium-channel blocker; and not better accounted for by another diagnosis (24). The presumed cause is contact between a blood vessel and the vestibular nerve in the cerebellopontine angle, although imaging studies reveal such a contact in as many as 45% of normal individuals (e15, e16). For the latter reason, MRI in this condition is indicated mainly to rule out other etiologies. A randomized, controlled trial demonstrated the significant therapeutic efficacy of oxcarbazepine at a dosage of 900 mg/day (attack frequency halved), although poor tolerability of the drug led to a 60% dropout rate (25). Lacosamide (100–200 mg/day) seems to be a well-tolerated alternative, as individual cases of off-label use have shown (26).
Third mobile window syndromes (semicircular canal dehiscence and, rarely, perilymph fistula)
The main manifestations of third mobile window syndromes are recurrent attacks of vertigo induced by changes in intracranial/middle-ear pressure or loud noises, autophony, increased bone conduction, and/or pulsatile tinnitus. Dehiscence of the superior semicircular canal is the most common subtype and is caused by a bony defect between the superior semicircular canal and the middle cranial fossa (Figure 3), creating a “third window” in the inner ear (in addition to the round and oval windows) (27). Alongside the clinical history, the diagnosis is based on a combination of at least one test finding typical of this syndrome, e.g., elevated amplitudes and/or reduced thresholds of cervical/ocular vestibular evoked myogenic potentials (VEMP) (e17), and high-resolution computer tomographic imaging of the petrous bone (slice thickness ≤ 0.6 mm). It is important to note that on CT about 2% of healthy subjects also show a thin bone on top of the superior canal.
For patients with mild symptoms, it usually suffices to explain the mechanism of the disease to them and for them to avoid marked pressure changes. For patients who are more severely impaired, surgical treatment is available (27).
Central vestibular syndromes
Central vestibular syndromes (e18) can manifest themselves as follows:
- Spinning vertigo and/or instability of stance and/or gait, due to ischemic or inflammatory lesions of the brainstem or cerebellum
- Recurrent attacks, as in vestibular migraine or episodic ataxia type 2
- A persistent syndrome, as in cerebellar dizziness.
Acute central vestibular syndrome: ischemia of the brainstem or cerebellum
In the acute vestibular syndrome, the most important differential diagnosis of an acute peripheral vestibulopathy is a central lesion in the brainstem or cerebellum, usually due to a stroke. The following features point to a stroke as the more likely cause: age over 60 years, a history of arterial hypertension or diabetes mellitus, accompanying symptoms referable to the central nervous system, and spontaneous and acute onset of the symptoms for the first time ever. In the clinical examination, the clinician should look for skew deviation/vertical divergence of the eyes, in which the vertical position of one eye is higher than that of the other. Furthermore, the nature of the spontaneous nystagmus is very important: if it cannot be suppressed by fixation, it is not a spontaneous nystagmus due to a peripheral vestibular disorder. Important further clues indicating a central lesion are a normal head-impulse test and a vertical nystagmus as well as a head-shaking nystagmus beating in the opposite direction to the spontaneous nystagmus.
Acute central vestibular syndrome is an emergency calling for immediate referral to a hospital that has the relevant diagnostic imaging and, ideally, a stroke unit. It should be emphasized here that, in patients with acute central vestibular syndrome due to a small stroke, MRI, including diffusion-weighted sequences, can often be normal in 50% of cases in the first 24 h (28). This underlines the importance of the patient’s history and clinical examination in determining the correct diagnosis.
Vestibular migraine is the most common cause of recurrent, spontaneous attacks of vertigo. Its 1-year prevalence is 2.7% among adults in the USA; the average age of individuals suffering from vestibular migraine is 40.9 years, and 64.1% of them are women (29). Vestibular migraine is defined as follows, according to the current diagnostic criteria (30):
- The patient has had at least five episodes of vestibular symptoms of moderate or severe intensity lasting from 5 min to 72 h.
- The patient has, or has had, migraine with or without aura as defined by the criteria of the International Classification of Headache Disorders (ICHD).
- At least 50% of the vestibular episodes are preceded by one or more migraine symptoms: headache with at least two of the following features (unilaterality, pulsatile character, moderate or severe intensity, aggravation by routine physical activities), photophobia, phonophobia, visual aura.
- The symptoms are not attributable to another vestibular or ICHD diagnosis.
A single one of the following two criteria suffices for the diagnosis of probable vestibular migraine: a history of migraine, or migraine symptoms during the attack.
The main differential diagnosis of vestibular migraine is Menière’s disease. Some patients meet the diagnostic criteria for both of these disorders; this suggests a pathophysiological link between them. Vestibular migraine might, for example, lead to a disturbance in the inner ear by way of the trigeminovascular system, increasing the probability of endolymphatic hydrops (e19). As there is no evidence yet to support any specific treatment for vestibular migraine (Cochrane Review ), this disorder should currently be treated like any other type of migraine.
Cerebellar dizziness and vertigo
Dizziness, vertigo, and imbalance due to cerebellar disease present a particular differential-diagnostic challenge. These patients typically do not present with the full spectrum of cerebellar symptoms. The entity of “cerebellar dizziness and vertigo” was, therefore, investigated more precisely in a study encompassing 369 patients (32), 81% of whom suffered from persistent dizziness, 31% from attacks of vertigo or dizziness, and 21% from both. Ninety-five percent had signs of a central ocular motor disorder (e.g., saccadic smooth pursuit, omnidirectional gaze-evoked nystagmus, central fixation nystagmus, and, in particular, downbeat nystagmus). The diagnosis cerebellar dizziness/vertigo is clinically relevant because many types can be treated with drugs, e.g., episodic ataxia type 2 (e20) and downbeat nystagmus (e21) with 4-aminopyridine, or certain other types of ataxia with acetyl-DL-leucine (33, 34).
Somatoform/psychogenic vertigo has been internationally designated as functional dizziness since 2017 and is probably the single most common type of vertigo (Figure); the term covers several subtypes, including phobic postural dizziness or persistent postural-perceptual dizziness. The Bárány Society, on the basis of many years of experience and in view of the many common features of phobic postural vertigo (phobischer Schwankschwindel) (e22) in Germany, chronic subjective dizziness in the USA, and visual vertigo in the UK (35), has established another entity called “persistent postural-perceptual dizziness” (PPPD) (36). This disorder is characterized by persistent dizziness and/or unsteadiness on most days over a period of 3 months or longer, with the symptoms lasting for hours per day, but not necessarily the whole day. The symptoms arise spontaneously but may be worsened by upright posture, active or passive body movements, or exposure to moving visual stimuli. Acute or chronic organic vestibular disorders, neurological or medical illness, or psychological distress may precede these symptoms, appear simultaneously with them, and/or outlast them. The symptoms cause marked functional impairment. They cannot be better explained by any other diagnosis.
Patients often complain of more or less permanent imbalance or light-headedness, which is usually less severe during sporting activities, on distraction, after the consumption of a small amount of alcohol, or in the morning, but is exacerbated by certain situations (e.g., in a crowd or in a department store); this can lead to avoidance behavior (“phobic postural dizziness”). Functional dizziness can be pathophysiologically explained as a result of heightened self-observation of balance. It typically affects individuals with perfectionist personality traits. As many as 45% of patients have an organic disease before the onset of symptoms: this condition is called secondary functional dizziness.
A detailed diagnostic evaluation is part of the effective treatment of this disorder. The work-up frees the patient from the fear that the symptoms are due to an underlying organic disease. Moreover, the treating physician should provide psychoeducation by explaining the mechanism of the disorder to the patient. The physician should encourage the patient to participate in sporting activities regularly, and a course of vestibular rehabilitation may be advisable (37). Both of these measures help the patient regain confidence in his or her own ability to maintain balance. If necessary, cognitive behavioral therapy or desensitization by auto-exposure can be performed. In the event of accompanying anxiety or simultaneous panic attacks, treatment with a selective serotonin reuptake inhibitor (38) or other antidepressants may be beneficial.
Approximately 70% of the affected patients can be treated successfully in this manner. There have not yet been any prospective, controlled trials of the treatment of this disorder (39).
The diagnostic evaluation of vestibular disorders
This is based on a combination of the clinical history with four key questions, physical examination of the vestibular, ocular motor, and cerebellar systems, a video head-impulse test, and, if the latter is normal, caloric testing.
The incidence of vertigo and dizziness is approximately 11% per year.
The diagnostic assessment has been simplified by the current classification of vestibular disorders of the Bárány Society (www.jvr-web.org/ICVD.html).
In the physical examination, special attention should be paid to spontaneous or positionally induced nystagmus. M glasses are a simple, practical aid to nystagmus testing.
The six most common peripheral vestibular syndromes, in order of
Important clues to the diagnosis are to be sought in the temporal course of the symptoms, any accompanying symptoms, and precipitating or modulating factors.
The differential diagnosis of common vestibular
Benign paroxysmal positional vertigo, Menière’s disease, acute unilateral vestibulopathy/vestibular neuritis, bilateral vestibulopathy, vestibular paroyxsmia, and the third mobile window syndromes.
Acute unilateral vestibulopathy/vestibular neuritis
Acute unilateral vestibulopathy is characterized by spinning vertigo that arises acutely and lasts for days to weeks, peripheral vestibular horizontal-torsional spontaneous nystagmus, a pathological head-impulse test, and the exclusion of an acute central vestibular syndrome.
Treatment recommendation for acute
The treatment of choice is steroid administration as soon as possible after the onset of symptoms, combined with balance training to reinforce central compensation.
Benign paroxysmal positional vertigo of the horizontal semicircular canal
Benign paroxysmal positional vertigo can be well treated by properly performed positioning maneuvers. Patients should, however, always be asked to give feedback concerning the outcome of treatment. If symptoms persist, further follow-up is indicated.
Benign paroxysmal positional vertigo
Benign paroxysmal positional vertigo of the horizontal canal is much rarer. It causes linear, horizontal nystagmus.
Pathogenesis of Menière’s disease
The pathogenesis of Menière’s disease is thought to involve a multifactorial disequilibrium of inner-ear homeostasis, of which endolymphatic hydrops is the final common pathway.
Betahistine in a dose of 48 or 144 mg/d is not superior to placebo, according to a randomized, controlled trial on 221 patients in which a strong placebo effect was found.
Acute vestibular syndrome
Vestibular paroxysmia consists of recurrent (as many as 100 times per day), spontaneously arising, brief attacks of vertigo. The demonstration of neurovascular conflict by MRI is not specific to this entity. A convincing response to a sodium-channel blocker supports the diagnosis.
In acute vestibular syndrome, the most important differential diagnosis of an acute peripheral vestibulopathy is a central lesion in the brainstem or cerebellum, usually due to a stroke.
Cerebellar dizziness and vertigo
The key to this diagnosis is the examination of eye movements, as practically all patients have at least one oculomotor abnormality of cerebellar origin, such as saccadic ocular pursuit, gaze-evoked nystagmus, or downbeat nystagmus.
Functional dizziness is probably the single most common vestibular syndrome. It can usually be diagnosed easily on the basis of the current “positive” diagnostic criteria, and its treatment after correct diagnosis is often successful.
Conflict of interest statement
Prof. Strupp owns stock in Intra Bio, as well as related patents. He serves as a paid consultant for Abbott, Actelion, AurisMedical, Heel, IntraBio, and Sensorion. He has received lecture honoraria from Abbott, Actelion, Auris Medical, Biogen, Eisai, Grünenthal, GSK, Hennig Pharma, Interacoustics, MSD, Mylan, Otometrics, Pierre-Fabre, TEVA, and UCB. He has received financial support from Abbott, Decibel Interacoustics, and Natus for a research project that he initiated, as well as third-party research support from Auris Medical, Biogen, Decibel, and Heel. He is the distributor of the M glasses.
Prof. Dlugaiczyk has received reimbursement of meeting participation fees and of travel and accommodation expenses from Hennig Arzneimittel and Otometrics, and lecture honoraria from Otometrics. She has received financial support for the performance of clinical studies from Otonomy.
Prof. Ertl-Wagner has a personal relationship with Siemens Healthineers.
Prof. Westhofen has received reimbursement of travel and accommodation expenses from Hennig Arzneimittel and lecture honoraria from Heel. His institution received financial support for a research project from Otonomy, and materials support for another study from Diatec/Interacoustics.
Prof. Dieterich has received financial support for the performance of clinical studies from Schwabe and Heel.
Prof. Rujescu states that he has no conflict of interest.
Manuscript received on 11 May 2019, revised version accepted on 16 October 2019.
Translated from the original German by Ethan Taub, M.D.
Prof. Dr. med. Dr. h.c. Michael Strupp, FRCP, FANA, FEAN
Neurologische Klinik und Deutsches Zentrum für Schwindel und Gleichgewichtsstörungen
Ludwig-Maximilians-Universität, München, Campus Grosshadern
Marchioninistr.15, 81377 München, Germany
Cite this as:
Strupp M, Dlugaiczyk J, Ertl-Wagner BB, Rujescu D, Westhofen M,
Dieterich M: Vestibular disorders—diagnosis, new classification and treatment.
Dtsch Arztebl Int 2020; 117: 300–10. DOI: 10.3238/arztebl.2020.0300
For eReferences please refer to:
Case illustration, eTables, eFigures:
Prof. Dr. med. Marianne Dieterich
German Center for Dizziness and Balance Disorders, Ludwig Maximilians University, Munich (LMU): Prof. Dr. med. Michael Strupp, Prof. Dr. med. Julia Dlugaiczyk,
Prof. Dr. med. Marianne Dieterich
Medical Imaging, University of Toronto, Canada: Prof. Dr. med. Birgit Bettina Ertl-Wagner
University Clinic and Outpatient Department for Psychiatry, Psychotherapy and Psychosomatics, University of Halle-Wittenberg: Prof. Dr. med. Dan Rujescu
Department of Otorhinolaryngology and Plastic Head and Neck Surgery, University Medical Center, RWTH Aachen, Prof. Dr. med. Martin Westhofen
Munich Cluster for Systems Neurology (SyNergy), Munich: Prof. Dr. med. Marianne Dieterich
|1.||Corrales CE, Bhattacharyya N: Dizziness and death: an imbalance in mortality. Laryngoscope 2016; 126: 2134–6 CrossRef MEDLINE|
|2.||Strupp M, Fischer C, Hanss L, Bayer O: The takeaway frenzel goggles: a fresnel-based device. Neurology 2014; 83: 1241–5 CrossRef MEDLINE PubMed Central|
|3.||Yip CW, Glaser M, Frenzel C, Bayer O, Strupp M: Comparison of the bedside head-impulse test with the video head-impulse test in a clinical practice setting: a prospective study of 500 outpatients. Front Neurol 2016; 7: 58 CrossRef MEDLINE PubMed Central|
|4.||Strupp M, Mandala M, Lopez-Escamez JA: Peripheral vestibular disorders: an update. Curr Opin Neurol 2019; 32: 165–73 CrossRef MEDLINE|
|5.||Strupp M, Kim JS, Murofushi T, et al.: Bilateral vestibulopathy: diagnostic criteria consensus document of the Classification Committee o f the Barany Society. J Vestib Res 2017; 27: 177–89 CrossRef MEDLINE|
|6.||Lucieer F, Vonk P, Guinand N, Stokroos R, Kingma H, van de Berg R: Bilateral vestibular hypofunction: insights in etiologies, clinical subtypes, and diagnostics. Front Neurol 2016; 7: 26 CrossRef MEDLINE PubMed Central|
|7.||Hall CD, Herdman SJ, Whitney SL, et al.: Vestibular rehabilitation for peripheral vestibular hypofunction: an evidence-based clinical practice guideline: from the American Physical Therapy Association Neurology Section. J Neurol Phys Ther 2016; 40: 124–55 CrossRef MEDLINE PubMed Central|
|8.||Dunlap PM, Holmberg JM, Whitney SL: Vestibular rehabilitation: advances in peripheral and central vestibular disorders. Curr Opin Neurol 2019; 32: 137–44 CrossRef MEDLINE|
|9.||Strupp M, Magnusson M: Acute unilateral vestibulopathy. Neurol Clin 2015; 33: 669–85 CrossRef MEDLINE|
|10.||Rujescu D, Hartmann AM, Giegling I, et al.: Genome-wide association study in vestibular neuritis: involvement of the host factor for HSV-1 replication. Front Neurol 2018; 9: 591 CrossRef MEDLINE PubMed Central|
|11.||Strupp M, Zingler VC, Arbusow V, et al.: Methylprednisolone, valacyclovir, or the combination for vestibular neuritis. N Engl J Med 2004; 351: 354–61 CrossRef MEDLINE|
|12.||Sjogren J, Magnusson M, Tjernstrom F, Karlberg M: Steroids for acute vestibular neuronitis-the earlier the treatment, the better the outcome? Otol Neurotol 2019; 40: 372–4 CrossRef MEDLINE PubMed Central|
|13.||von Brevern M, Bertholon P, Brandt T, et al.: Benign paroxysmal positional vertigo: diagnostic criteria. J Vestib Res 2015; 25: 105–17 CrossRef MEDLINE|
|14.||Bhattacharyya N, Gubbels SP, Schwartz SR, et al.: Clinical practice guideline: benign paroxysmal positional vertigo (Update). Otolaryngol Head Neck Surg 2017; 156 (3_suppl): S1-S47 CrossRef MEDLINE|
|15.||Lopez-Escamez JA, Carey J, Chung WH, et al.: Diagnostic criteria for Meniere‘s disease. J Vestib Res 2015; 25: 1–7 CrossRef MEDLINE|
|16.||Attye A, Eliezer M, Medici M, et al.: In vivo imaging of saccular hydrops in humans reflects sensorineural hearing loss rather than Meniere‘s disease symptoms. Eur Radiol 2018; 28: 2916–22 CrossRef MEDLINE|
|17.||Adrion C, Fischer CS, Wagner J, Gurkov R, Mansmann U, Strupp M: Efficacy and safety of betahistine treatment in patients with Meniere‘s disease: primary results of a long term, multicentre, double blind, randomised, placebo controlled, dose defining trial (BEMED trial). BMJ 2016; 352: h6816 CrossRef MEDLINE MEDLINE|
|18.||Hussain K, Murdin L, Schilder AG: Restriction of salt, caffeine and alcohol intake for the treatment of Meniere‘s disease or syndrome. Cochrane Database Syst Rev 2018; 12: CD012173 CrossRef MEDLINE PubMed Central|
|19.||Thirlwall AS, Kundu S: Diuretics for Meniere‘s disease or syndrome. Cochrane Database Syst Rev 2006; 3: CD003599.|
|20.||Pullens B, Verschuur HP, van Benthem PP: Surgery for Meniere‘s disease. Cochrane Database Syst Rev 2013; 2: CD005395 CrossRef MEDLINE|
|21.||Tighilet B, Leonard J, Watabe I, Bernard-Demanze L, Lacour M: Betahistine treatment in a cat model of vestibular pathology: pharmacokinetic and pharmacodynamic approaches. Front Neurol 2018; 9: 43 CrossRef MEDLINE PubMed Central|
|22.||Schoo DP, Tan GX, Ehrenburg MR, Pross SE, Ward BK, Carey JP: Intratympanic (IT) Therapies for Meniere‘s Disease: some consensus among the confusion. Curr Otorhinolaryngol Rep 2017; 5: 132–41 CrossRef MEDLINE PubMed Central|
|23.||Brandt T, Dieterich M: Vestibular paroxysmia: vascular compression of the eighth nerve? Lancet 1994; 343: 798–9 CrossRef|
|24.||Strupp M, Lopez-Escamez JA, Kim JS, et al.: Vestibular paroxysmia: diagnostic criteria. J Vestib Res 2016; 26: 409–15 CrossRef MEDLINE|
|25.||Bayer O, Bremova T, Strupp M, Hufner K: A randomized double-blind, placebo-controlled, cross-over trial (Vestparoxy) of the treatment of vestibular paroxysmia with oxcarbazepine. J Neurol 2018; 265: 291–8 CrossRef MEDLINE PubMed Central|
|26.||Strupp M, Elger C, Goldschagg N: Treatment of vestibular paroxysmia with lacosamide. Neurol Clin Pract 2019; 9: 539–41 CrossRef MEDLINE|
|27.||Ward BK, Carey JP, Minor LB: Superior canal dehiscence syndrome: lessons from the first 20 years. Front Neurol 2017; 8: 177 CrossRef MEDLINE PubMed Central|
|28.||Saber Tehrani AS, Kattah JC, Kerber KA, et al.: Diagnosing stroke in acute dizziness and vertigo: pitfalls and pearls. Stroke 2018; 49: 788–95 CrossRef MEDLINE PubMed Central|
|29.||Formeister EJ, Rizk HG, Kohn MA, Sharon JD: The epidemiology of vestibular migraine: a population-based survey study. Otol Neurotol 2018; 39: 1037–44 CrossRef MEDLINE|
|30.||Lempert T, Olesen J, Furman J, et al.: Vestibular migraine: diagnostic criteria. J Vestib Res 2012; 22: 167–72 CrossRef MEDLINE|
|31.||Maldonado FM, Birdi JS, Irving GJ, Murdin L, Kivekas I, Strupp M: Pharmacological agents for the prevention of vestibular migraine. Cochrane Database Syst Rev 2015; 6: CD010600.|
|32.||Feil K, Strobl R, Schindler A, et al.: What is behind cerebellar vertigo and dizziness? Cerebellum 2019; 18: 320–32 CrossRef MEDLINE|
|33.||Strupp M, Teufel J, Zwergal A, Schniepp R, Khodakhah K, Feil K: Aminopyridines for the treatment of neurologic disorders. Neurology: Clinical Practice 2017; 7: 65–76 CrossRef MEDLINE PubMed Central|
|34.||Kalla R, Strupp M: Aminopyridines and acetyl-DL-leucine: new therapies in cerebellar disorders. Curr Neuropharmacol 2019; 17: 7–13 CrossRef MEDLINE PubMed Central|
|35.||Dieterich M, Staab JP: Functional dizziness: from phobic postural vertigo and chronic subjective dizziness to persistent postural-perceptual dizziness. Curr Opin Neurol 2017; 30: 107–13 CrossRef MEDLINE|
|36.||Staab JP, Eckhardt-Henn A, Horii A, et al.: Diagnostic criteria for persistent postural-perceptual dizziness (PPPD): consensus document of the Committee for the Classification of Vestibular Disorders of the Barany Society. J Vestib Res 2017; 27: 191–208 CrossRef MEDLINE|
|37.||Nada EH, Ibraheem OA, Hassaan MR: Vestibular rehabilitation therapy outcomes in patients with persistent postural-perceptual dizziness. Ann Otol Rhinol Laryngol 2019; 128: 323–9 CrossRef MEDLINE|
|38.||Yu YC, Xue H, Zhang YX, Zhou J: Cognitive behavior therapy as augmentation for sertraline in treating patients with persistent postural-perceptual dizziness. Biomed Res Int 2018; 2018: 8518631 CrossRef MEDLINE PubMed Central|
|39.||Popkirov S, Stone J, Holle-Lee D: Treatment of persistent postural-perceptual dizziness (PPPD) and related disorders. Curr Treat Options Neurol 2018; 20: 50 CrossRef MEDLINE|
|e1.||Neuhauser HK: The epidemiology of dizziness and vertigo. Handb Clin Neurol 2016; 137: 67–82 CrossRef MEDLINE|
|e2.||Hulse R, Biesdorf A, Hormann K, et al.: Peripheral vestibular disorders: an epidemiologic survey in 70 million individuals. Otol Neurotol 2019; 40: 88–95 CrossRef MEDLINE|
|e3.||Halmagyi GM, Chen L, MacDougall HG, Weber KP, McGarvie LA, Curthoys IS: The video head impulse test. Front Neurol 2017; 8: 258 CrossRef MEDLINE PubMed Central|
|e4.||Lehnen N, Kellerer S, Knorr AG, et al.: Head-movement-emphasized rehabilitation in bilateral vestibulopathy. Front Neurol 2018; 9: 562 CrossRef MEDLINE PubMed Central|
|e5.||Feil K, Feuerecker R, Goldschagg N, et al.: Predictive capability of an iPad-Based Medical Device (medx) for the diagnosis of vertigo and dizziness. Front Neurol 2018, 9: 29 CrossRef MEDLINE PubMed Central|
|e6.||Shah MU, Lotterman S, Roberts D, Eisen M: Smartphone telemedical emergency department consults for screening of nonacute dizziness. Laryngoscope 2019; 129: 466–9 CrossRef MEDLINE|
|e7.||Park MK, Lee DY, Kim YH: Risk factors for positional vertigo and the impact of vertigo on daily life: The Korean National Health and Nutrition Examination Survey. J Audiol Otol 2019; 23: 8–14 CrossRef MEDLINE PubMed Central|
|e8.||Kim SK, Hong SM, Park IS, Choi HG: Association between migraine and benign paroxysmal positional vertigo among adults in South Korea. JAMA Otolaryngol Head Neck Surg 2019; 145: 307–12 CrossRef MEDLINE PubMed Central|
|e9.||Sim E, Tan D, Hill K: Poor treatment outcomes following repositioning maneuvers in younger and older adults with benign paroxysmal positional vertigo: a systematic review and meta-analysis. J Am Med Dir Assoc 2019; 20: 224 CrossRef MEDLINE|
|e10.||Tse D, Ramsay T, Lelli DA: Novel use of portable audiometry to track hearing fluctuations in Meniere‘s disease: a pilot study. Otol Neurotol 2019; 40: e130–e4 CrossRef MEDLINE|
|e11.||Frejo L, Martin-Sanz E, Teggi R, et al.: Extended phenotype and clinical subgroups in unilateral Meniere disease: A cross-sectional study with cluster analysis. Clin Otolaryngol 2017; 42: 1172–80 CrossRef MEDLINE|
|e12.||Gurkov R, Kantner C, Strupp M, et al.: Endolymphatic hydrops in patients with vestibular migraine and auditory symptoms. Eur Arch Otorhinolaryngol 2104; 271: 2661–7 CrossRef MEDLINE|
|e13.||Lim MY, Zhang M, Yuen HW, Leong JL: Current evidence for endolymphatic sac surgery in the treatment of Meniere‘s disease: a systematic review. Singapore Med J 2015; 56: 593–8 CrossRef MEDLINE PubMed Central|
|e14.||Sood AJ, Lambert PR, Nguyen SA, Meyer TA: Endolymphatic sac surgery for Meniere‘s disease: a systematic review and meta-analysis. Otol Neurotol 2014; 35: 1033–45 CrossRef MEDLINE|
|e15.||Best C, Gawehn J, Kramer HH, et al.: MRI and neurophysiology in vestibular paroxysmia: contradiction and correlation. J Neurol Neurosurg Psychiatry 2013; 84: 1349–56 CrossRef MEDLINE|
|e16.||Sivarasan N, Touska P, Murdin L, Connor S: MRI findings in vestibular paroxysmia—an observational study. J Vestib Res 2019; 29: 137–45 CrossRef MEDLINE|
|e17.||Fife TD, Colebatch JG, Kerber KA, et al.: Practice guideline: cervical and ocular vestibular evoked myogenic potential testing: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology 2017; 89: 2288–96 CrossRef MEDLINE PubMed Central|
|e18.||Brandt T, Dieterich M: The dizzy patient: don‘t forget disorders of the central vestibular system. Nat Rev Neurol 2017; 13: 352–62 CrossRef MEDLINE|
|e19.||Nakashima T, Pyykko I, Arroll MA, et al. Meniere‘s disease. Nat Rev Dis Primers 2016; 2:16028 CrossRef MEDLINE|
|e20.||Strupp M, Kalla R, Claassen J, et al.: A randomized trial of 4-aminopyridine in EA2 and related familial episodic ataxias. Neurology 2011; 77: 269–75 CrossRef MEDLINE PubMed Central|
|e21.||Claassen J, Spiegel R, Kalla R, et al.: A randomised double-blind, cross-over trial of 4-aminopyridine for downbeat nystagmus—effects on slowphase eye velocity, postural stability, locomotion and symptoms. J Neurol Neurosurg Psychiatry 2013; 84: 1392–9 CrossRef MEDLINE|
|e22.||Brandt T, Dieterich M. Phobischer Attacken-Schwankschwindel, ein neues Syndrom. Münch Med Wochenschr 1986; 128: 247–50.|
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