This review provides an update on interdisciplinary treatment for dizziness. Dizziness can have various causes and the treatment offered should depend on the cause. After reading this article, the clinician will have an overview of current treatment recommendations. Recommendations are made for the most prevalent causes of dizziness including acute and chronic vestibular syndromes, vestibular neuritis, benign paroxysmal positional vertigo, endolymphatic hydrops and Menière’s disease, vestibular paroxysmia and vestibular migraine, cardiac causes, transient ischaemic attacks and strokes, episodic ataxia type 2, persistent postural-perceptual dizziness, bilateral vestibulopathy, degenerative, autoimmune and neoplastic diseases, upbeat- and downbeat nystagmus. Recommendations include clinical approaches (repositioning manoeuvres), medication (adding, removing or changing current medication depending on aetiology), vestibular physiotherapy, ergotherapy and rehabilitation, treatment of chest pain or stroke units and surgical interventions. If symptoms are acute and severe, medication with antivertigo agents is recommended as a first step, for a maximum period of 3 days. Following initial symptom control, treatment is tailored depending on aetiology. To assist the clinician in obtaining a useful overview, the level of evidence and number needed to treat are reported whenever possible based on study characteristics. In addition, warnings about possible arrhythmias due to medication are issued, and precautions to enable these to be avoided are discussed.
Keywords : dizziness, emergency, vertigo, vestibular, HINTS
This review summarises treatment approaches for different types of vestibular syndromes with central and peripheral aetiologies. It relates to prior reviews [1–3] and adds recent developments in the field. It also complements the manuscript on diagnostic procedures for dizziness in the emergency department published in this journal . Where no studies exist, tentative recommendations based on clinical expertise are made. This review aims at providing an overview of currently available treatment strategies for clinicians of different disciplines. Even though specialist consultation might still be required, knowledge about current treatment options facilitates interdisciplinary dialogue.
Acute vestibular syndrome
An acute vestibular syndrome consists of an acute onset of dizziness associated with nystagmus, nausea, light-headedness and balance problems and lasting longer than 24 hours [5, 6]. In almost any acute vestibular syndrome, the following symptomatic treatment can be prescribed for the first 3 days: an antihistamine such as dimenhydrinate orally 50 mg every 4–6 hours or as a suppository 150 mg once or twice per 24 hours , an anticholinergic such as transdermal scopolamine 1 mg over 72 hours , a benzodiazepine such as diazepam orally 5–10 mg every 4–6 hours, or clonazepam orally 0.5 mg every 4–8 hours [1, 3]. Such medications should, however, not be taken for more than 3 days, because they are believed to inhibit central compensatory processes, and benzodiazepines have addictive potential . The evidence for recommending these three medications for symptomatic treatment is rather weak. It is based on expert opinion. On the other hand, experts have observed thousands of patients in the German Dizziness Center. For the future, it is necessary to perform prospective, comparative studies that permit the calculation of a number needed to treat.
Before prescribing dimenhydrinate, an electrocardiogram (ECG) should be recorded. A second ECG should be recorded after initiating treatment with dimenhydrinate, because it can cause a prolongation of the frequency corrected QT interval. Consequently, there is the danger of the Torsade-de-pointes arrhythmia, especially if the patient has a congenital or acquired long QTc interval, is also taking other potentially QTc prolonging drugs in addition to dimenhydrinate, or has other risk factors such as low serum potassium levels. No absolute risk numbers can be provided, though, because patients with long QTc syndrome are excluded from studies with QTc-prolonging agents. To avoid putting patients at risk, we recommend an ECG. It is particularly important to avoid combining QTc-prolonging drugs. Instead, treatment alternatives should be considered.
It is noteworthy that benzodiazepines themselves can be the cause of dizziness. Moreover, the combination of different benzodiazepines is discouraged. Antihistamines, anticholinergics and benzodiazepines are also referred to as antivertiginosa . Prior to prescribing them, however, the primary care physician can try to alleviate the symptoms by other means. For example, if the patient suffers from benign paroxysmal positional vertigo, a repositioning manoeuvre is indicated. Examples of how to carry out this manoeuvre are described in this review. If the primary care physician cannot manage the symptoms, antivertiginosa can be applied to treat acute episodes of dizziness . Although we are not aware of comparative trials that make exact reference to the number of days for which they should be administered, we suggest a prescription over a maximum of 3 days in the recommended doses of dimenhydrinate, scopolamine and clonazepam [1, 3]. Although the aim must be to refer the patient to the specialist as fast as possible if treatment attempts by the emergency physician fail, not all patients get an immediate appointment. In such a case, antivertiginosa are a good choice to control the symptoms. Once the patient has seen the specialist, the right diagnosis can be made and the treatment with antivertiginosa can be stopped in favour of another treatment.
Acute unilateral vestibulopathy
An acute vestibular syndrome in which drug therapy might be useful is acute unilateral vestibulopathy [1–3, 7–9]. A detailed overview of the symptoms of an acute vestibular syndrome is described in the accompanying article on diagnosis . Dizziness is often linked to an oscillating visual perception (oscillopsia), nausea, postural instability and ataxia. The cause may be re-activation of herpes simplex virus type 1 in the vestibular ganglia [1–3, 8, 9], although there is no definite proof for this hypothesis [1–3].
To control acute symptoms, antivertiginosa [1–3, 8] can be applied as described above. If the cochlea or the vestibulocochlear nerve is involved (also known as labyrinthitis), this condition can be associated with hearing loss. In this case, the patient should be referred to an ear, nose and throat specialist. The vestibular nerve lies in a bony canal and nerve ischaemia due to inflammation-related swelling can be reduced by administration of methylprednisolone; thereby vestibular function may recover [1–3, 10–13]. The level of evidence in these studies ranges from 1  to 3 [11, 13]. The number needed to treat ranges between two and three in all three studies for corticosteroid treatment versus no treatment. Note that one study  had no no-treatment group, so the exact number needed to treat can only be estimated from other studies on how many patients without treatment have spontaneous remission. It is noteworthy that a 6-month follow-up showed no superiority of corticosteroids over physical therapy , with even a slight advantage for physical therapy over corticosteroid treatment (level of evidence 1, number needed to treat 20). Methylprednisolone should be administered in a daily oral dose of 100 mg and this dose should be reduced by 20 mg every fourth day [1–3]. Alternatively, prednisolone can be administered. During treatment, patients’ blood sugar levels should be monitored. The risk for gastric ulcers should be considered. If the patient has a risk factor for gastric ulcers and if there is co-medication with non-steroidal anti-inflammatory drugs or a high bleeding risk due to platelet inhibitors or a therapeutic anticoagulation regimen in addition to cortisone, the administration of a proton pump inhibitor should be considered. We also recommend that patients at risk for osteoporosis receive a calcium and vitamin D supplement, such as 1000 mg of calcium and 800 IU of vitamin D daily.
There is evidence that physiotherapy, which can foster central vestibular compensatory mechanisms [1–3], additionally helps to control symptoms and is at least, if not more effective, than corticosteroid treatment . In particular, there is evidence for significant symptom reduction following vestibular physiotherapy [8, 12, 14–21]. Vestibular physiotherapy can help to train balance in uni- or bilateral peripheral disorders or in visual vertigo [14–18]. Therefore, physiotherapy should be initiated at first presentation. We consider physiotherapy to be at least as important as pharmacotherapy. It is, however, necessary that the patient sees a physiotherapist who is specialised in vestibular physiotherapy. Depending on the healthcare system, it may be necessary to explicitly mention vestibular physiotherapy on the prescription.
Acute vestibular syndrome can also be caused by central aetiologies, with cerebellar stroke being the most common central cause .
Cerebellar stroke can mimic the signs of peripheral vestibulopathy. Downbeat nystagmus is present in about 50% of cerebellar strokes [22, 23]. Consequently, a cerebellar infarction should always be considered as a differential diagnosis, even if peripheral vestibulopathic failure is suspected . As in brainstem strokes, gaze-evoked nystagmus is a sensitive sign of a lesion within the cerebellum [22, 24]. If recognised within the appropriate time-frame and after exclusion of contraindications, thrombolysis is indicated. Therefore, a neurologist should be involved if stroke remains among differential diagnoses during initial evaluation. If indicated, an intravenous or intra-arterial thrombolytic agent should be administered within the first 4.5  to 6 hours . Intravenous thrombolysis consists of systemic administration of recombinant tissue plasminogen activator to re-perfuse thrombotic occlusions. Intra-arterial thrombolysis requires a catheter to be placed near the thrombotic occlusion, with the aim of achieving thrombolysis at the location of the blocked artery. Studies and recommendations on thrombolysis, however, are subject to continuous re-evaluation. There are cases where patients benefit from thrombolysis even beyond 6 hours after symptom onset. It is noteworthy that some patients often have no symptoms other than dizziness, nystagmus and imbalance . For this reason, it is important to recognise the symptoms and to correctly classify them as central rather than peripheral causes. Even if no stroke is present, auditary and vestibular loss can reflect a significant stenosis of the anterior inferior cerebellar artery [22, 26, 27] and precede an imminent stroke [22, 26, 27].
Patients with isolated hearing loss or dizziness may have a labyrinthine stroke, as the inner ear receives its blood supply from the vertebrobasilar system . Labyrinthine stroke or stenosis of the internal auditory artery may not be recognised with magnetic resonance imaging (MRI) . The labyrinthine artery is a branch of the anterior inferior cerebellar artery (AICA). Typical symptoms of an infarction are sudden onset of unilateral deafness and vertigo. A variety of structures can be affected by occlusion of the AICA, such as the posterolateral pons, cranial nerve nuclei (V, VII, VIII [vestibular, cochlear]) and fascicles (VII, VIII), the sympathetic tract, the spinothalamic tract, the middle cerebellar peduncle . To our knowledge there are only small case series reporting this pseudo-labyrinthitis type of infarction (e.g. ). As far as we are aware, no studies have been conducted to date to detect the frequency of labyrinthine stroke. As it combines clinical features of peripheral and central signs and is not detectable via MRI, it is challenging to diagnose. One has to consider this kind of stroke in elder patients with cardiovascular risk factors .
Whenever a significant stenosis is suspected, for example because of repeated transient ischaemic attacks, an analysis of the blood vessels with either computed tomography (CT) or MRI angiography is mandatory [22, 31–33]. On one hand, it is important to recognise present or imminent stroke to reduce the damage resulting from ischaemia; on the other hand this treatment might itself result in harmful consequences [34–36]. If a transient ischaemic attack or stroke is suspected, the start of treatment was linked to an 80% risk reduction of additional disability due to a subsequent stroke . This does not mean that all patients need thrombolysis, but it means that the transient ischaemic attack or stroke is recognised and treatment is initiated, for example by beginning treatment with platelet inhibitors, oral anticoagulants or a statin . In order to recognise significant stenoses, CT- or MR-angiography is necessary and patients should be referred to centres where it is available. Harmful consequences and risks of diagnostic tests and treatment, such as contrast-induced nephropathy, need to be considered. Not all patients will be candidates for systemic thrombolysis, for example patients with isolated vertigo, which results in a zero value in the National Institutes of Health Stroke Scale. The risk of systemic thrombolysis includes potentially fatal intracranial haemorrhages, which occur in 2% of patients within the first couple of days after its application . As an initial guide as to whether the patient suffers from a stroke, several clinical tests have proved useful. They are described in our accompanying manuscript on diagnosis and elsewhere [4, 5, 22, 37–40].
Episodic vestibular syndromes
An episodic vestibular syndrome is defined as dizziness lasting less than 24 hours. Consequently, it may consist of a short episode or repeated short episodes. It can be associated with nausea, balance problems, nystagmus or motion intolerance . A prominent example of an episodic vestibular syndrome is benign paroxysmal positional vertigo, which will be described in the next section.
Benign paroxysmal positional vertigo and repositioning manoeuvres
The most important therapeutic procedures to treat benign paroxysmal positional vertigo, where otolithic debris is moving inside a canal (canalolithiasis) [3, 42–46] or inside/near the cupula (cupulolithiasis) [42, 47–49], are repositioning manoeuvres. The majority of benign paroxysmal positional vertigo is idiopathic. Known causal factors include ototoxic medication , prolonged bed rest , cervical hyperextension , osteoporosis [53, 54], age , and migraine . There are leaflets for treatments and prophylaxis of some of these conditions, such as osteoporosis and migraine.
There are four types of benign paroxysmal positional vertigo, depending on the involvement of a specific semicircular canal. Diagnostic manoeuvres to identify the affected canal are summarised in table 1, repositioning manoeuvres in figure 1. The most commonly involved semicircular canals are the posterior ones  (90%). Note that repositioning manoeuvres should be performed by trained individuals, since an incorrectly applied manoeuvre might induce an iatrogenic switch or conversion of the affected canal, for example from a posterior benign paroxysmal positional vertigo to a horizontal benign paroxysmal positional vertigo [69–71]. Otolith repositioning should only be performed after determination of the affected canal by means of diagnostic positioning techniques. A detailed overview of other individual manoeuvres can be found in the literature . In addition, figures 1A and 1B show the correct head and body positions during repositioning manoeuvres of the posterior semicircular canal.
|Affected semicircular canal||Repositioning manoeuvre [3, 45–47, 49, 57, 58]|
|Posterior (Barany 1921 )||Epley |
|Horizontal geotropic (Mac Clure 1985 )||Barbecue, Gufoni for geotropic form [46, 63]|
|Horizontal apogeotropic (Baloh et al. 1995 )||Gufoni for ageotropic form |
|Anterior (Bertholon et al. , Califano et al. 2014 )||Canalith repositioning technique (CRT) |
Endolymphatic hydrops and Menière’s disease
Among the different episodic vestibular syndromes, Menière’s disease has been extensively studied [1–3, 72–101]. It is characterised by recurrent attacks of dizziness, hearing loss and the sensation of ear pressure, as well as tinnitus, probably due to an endolymph hydrops (overproduction or under-resorption of endolymph) [1–3, 89, 90]. As a result, there is recurrent leakage through the membrane separating endolymph and perilymph spaces [1–3]. Hence, the therapeutic goal is to reduce the production or to enhance the absorption of endolymph [1–3]. The degree of individual suffering can sometimes appear alarming when the patient first presents to medical staff . So far, there are more than 6000 articles on Menière’s disease. Articles cover a wide spectrum of therapeutic recommendations [1–3, 72–94, 96–101]. The treatment of Menière’s disease consists of several steps depending on the stage and severity of disease . The therapeutic goal is to reduce the number of attacks in order to prevent future vestibular deficits . Conservative treatments include salt restriction or the administration of diuretics [1–3, 72–74, 92]. Whereas some authors recommend that therapy can be initiated with salt restriction followed by diuretics , others doubt the benefits of this treatment approach and warn of potentially harmful consequences [73, 74] of salt restriction or diuretics. In our opinion, this approach is not recommended. Other conservative treatments include the administration of an H1-agonist/H3-antagonist (betahistine dihydrochloride) or its metabolites [72, 75–79, 91–94]. Betahistine dihydrochloride improves microcirculation in the inner ear, resulting in better balance between endolymph production and resorption [1, 2, 76–78, 91]. Although a recently published long-term, multicentre, double-blind, randomised, placebo-controlled study did not find evidence for successful symptom control with betahistine dihydrochloride , other results, including data from a meta-analysis , suggest symptom control after betahistine dihydrochloride administration [1–3, 79, 92–94]. Based on clinical experience with 112 patients over a period of 12 months, it is recommended to administer 48 mg betahistine dihydrochloride orally three times daily [1–3, 93]. In individual cases, this dose can be increased up to 480 mg daily if no sufficient symptom alleviation is achieved after 3 months of treatment [1, 94].
As a second step, more invasive treatments, such as intratympanic steroid injections, may be considered [1, 2, 80, 81, 96–99]. Such treatments, although invasive, still have low complication rates and minimal side effects [1, 2]. Intratympanic instillations of 0.4–1 ml high-dose dexamethasone solution (12 mg/ml)  might also be effective [1, 2, 99, 102]. Double-blind, placebo-controlled trials demonstrated symptom reduction following intratympanic steroid injection [81, 96]. In contrast to an aminoglycoside instillation (see third step below), however, it is not associated with hearing loss [1, 2, 80, 81, 96–99].
As a third step, more invasive options are reserved for patients with intractable Menière's disease. Chemoablative agents, such as gentamicin, proved successful in reducing the attacks of Menière's disease [1–3, 82, 84, 85, 90, 101]. Its obvious downside is possible hearing loss , which is the reason why it is recommended in patients with pre-existing hearing loss. New protocols with low-dose fractioned transtympanic application of gentamicin (diluted gentamicin, 26.7 mg/ml, pH 6.4, weekly for 4 weeks) aim to reduce the risk of hearing loss [86, 90, 101]. Gentamicin damages the hair cells responsible for vestibular information in the inner ear . Hence, its prophylactic administration is associated with a decrease of attacks. It can also cause hearing loss owing to the proximity of other hair cells responsible for hearing. However, recently data from a randomised, double-blind, comparative effectiveness trial of intratympanic methylprednisolone versus gentamicin in patients with unilateral Menière´s disease failed to show a significant difference between gentamicin and methylprednisolone in controlling vertigo/dizziness . Surgical approaches are also discussed in the literature . Patients with hearing loss might benefit from labyrinthectomy, whereas patients with preserved hearing are candidates for selective vestibular neurectomy with hearing preservation . Other surgical procedures such as endolymphatic sac surgery are not recommended owing to lack of evidence of beneficial effects .
In summary, the more invasive methods such as gentamicin treatment or neurectomy are effective, but are also associated with risks and adverse effects. We recommend starting with the least invasive methods mentioned in step 1 and slowly progressing to more invasive options if the symptoms cannot be controlled otherwise. In any case, it is necessary to inform the patient about the risks and to make sure that invasive procedures are carried out by clinicians with the relevant experience. If the patient cannot be examined by a specialist immediately, clinicians without expertise regarding Menière’s disease should consider administering antivertiginosa or betahistine dihydrochloride. Subsequently, the clinicians should make sure that the patient is seen by a specialist.
Superior canal dehiscence syndrome
Superior canal dehiscence syndrome is an episodic vestibular syndrome [104–108]. It consists of dizziness combined with auditory symptoms such autophony, hyperacusis and tinnitus induced by sound or pressure. The reason for this pressure transmission is a bony dehiscence of the superior semicircular canal, first described by Minor in 1998 . Surgical repair such as capping, re-surfacing or plugging of the superior semicircular canal is recommended [106–108].
Drug therapy may alleviate symptoms of vestibular paroxysmia [1, 2], which characterised by recurrent attacks of spinning vertigo persisting up to 1 minute [1, 2]. Vestibular paroxysmia may rarely be accompanied by either tinnitus or decreased hearing . It often leads to unsteadiness of stance or gait and can be provoked by a change in head position or by hyperventilation [1, 109, 110]. Its origin is probably a compression of the eighth cranial nerve by blood vessels near the brainstem [1, 2, 109–112]. Recommended medications are oral carbamazepine 200–600 mg per day [1, 2, 110], in some cases up to 800 mg per day , or oxcarbazepine in slightly higher doses. The efficacy of oxcarbazepine to relieve symptoms was demonstrated in a group of patients who received a mean dose of 870 mg of per day . For both carbamazepine and oxcarbazepine, we recommend starting with a low dose and progressing slowly to higher doses. The weakness of these recommendations is that prospective, randomised comparative trials do not exist. Therefore, a number needed to treat cannot be computed. The following recommendations in this section rely on expert opinion (level of evidence 5). Consequently, prospective studies with comparative treatment arms are strongly encouraged.
If carbamazepine is not tolerated, there are alternatives, such as phenytoin, gabapentin or valproate, although these are not based on evidence [1, 2]. Patients therefore need to be informed of the off-label administration. We would also recommend considering potential side-effects and contraindications such as high-level atrioventricular block, bradycardia, electrolyte imbalances, etc. In our opinion, treatment should start with low doses: for example, in adults 100 mg phenytoin orally once daily, which can be subsequently increased up to three times per day (over the next four to six days, increasing the dose every two to three days). With gabapentin, the starting dose could be 300 mg once on day one, to be increased to twice daily on day two and three times daily on day three. Only in the case of partial yet insufficient symptom relief would we recommend a further increase. Because empirical evidence is lacking, we would not recommend a daily dose higher than 1800 mg. Valproate dosing, on the other hand, is more dependent on body weight. We would start with 10 mg per kilogram body weight, and increase the dose every three days to a maximum daily dose of 20 mg per kilogram body weight. Antiepileptic medications can themselves elicit dizziness [113, 114], so they should be administered cautiously. We would also recommend that they are prescribed only by a specialist who is able to differentiate possible side effects from the sensation of dizziness per se and who carries out the necessary laboratory checks. In particular, valproate can be associated with blood count changes such as leucopenia and thrombopenia or elevated liver enzymes.
Another episodic vestibular syndrome of central and peripheral origin is vestibular migraine. It is characterised by attacks of either dizziness alone or combined with stance and gait ataxia, headache, nausea, vomiting and visual sensations [1–3]. These episodes might last minutes to hours and can be first treated symptomatically with the previously mentioned antivertiginosa . The principles of migraine treatment can be applied to prevent attacks of vestibular migraine. We recommend prophylactic oral administration of topiramate 25–100 mg daily or valproate 300–900 mg daily [1, 115] or the sustained release form of metoprolol 50–200 mg daily [1, 116, 117]. There is no clear evidence for the benefits of zolmitriptan in vestibular migraine [117, 118], whereas positive effects were found for the prophylactic oral administration of propranolol 40–240 mg daily [117, 119], amitriptyline 50–100 mg daily [117, 120], flunarizine 5–10 mg daily [116, 117], and acetazolamide 250–750 mg daily [117, 121]. If the patient takes several medications, it is necessary to check for drug-drug interactions and to consider the QTc prolonging effect (see Introduction).
Cardiac causes and transient ischaemic attacks
Cardiac problems cause orthostatic dizziness, which can be treated with compression stockings, but the majority of cardiac causes identified in a systematic review were actually true vertigo . Hence, whenever patients report the sensation of dizziness, it is important to remember that this could be of cardiovascular, valvular or arrhythmic origin. In some cases, patients may benefit from revascularisation, valve repair/replacement or antiarrhythmic treatment. If atrial fibrillation has persisted for more than 48 hours, cardioversion into sinus rhythm should be attempted only after exclusion of an atrial thrombus by transoesophageal echocardiography.
As mentioned previously, stroke is also a potential cause of dizziness. The same holds true for transient ischaemic attacks, where patients may have isolated dizziness or other stroke symptoms for less than 24 hours and without acute ischaemic lesions on MRI. In addition, intermittent isolated vertigo may also be caused by vertebrobasilar insufficiency preceding a stroke [22, 26]. Patients who suffer a transient ischaemic attack should undergo MRI with MR-angiography, neurovascular ultrasonography to look for plaques or stenoses, echocardiography, and a long-term ECG to look for atrial fibrillation (if atrial fibrillation was not already present in the ECG upon admission) . Treatment of transient ischaemic attacks is usually a statin and aspirin . The most recent stroke prevention guidelines should be consulted  and vascular risk factors should be sought. If the patient is on a factor Xa inhibitor for atrial fibrillation and suffers from a transient ischaemic attack, anti-factor Xa activity should be determined as a therapy check. If the medication has insufficient effect, anticoagulant treatment should be changed. If the transient ischaemic attack occurs under previously established statin treatment, switching to another statin should be considered, because, apart from lipid levels, the plaque-stabilising effects of statins might differ. Thromboendarterectomy or stenting should be considered in the case of symptomatic stenoses such as subclavian artery stenosis or the rare cases of symptomatic carotid stenosis associated with dizziness .
Episodic ataxia type 2
There are a number of inherited syndromes with recurrent attacks of dizziness and ataxia [1–3, 124, 125]. Among these inherited syndromes, episodic ataxia type 2 is the most frequent . Symptoms are dizziness and ataxia lasting several hours, which are often elicited by physical activity, alcohol consumption or stress [1–3]. Over 90% of the patients have oculomotor disorders such as downbeat nystagmus . Successful treatment approaches include the administration of an aminopyridine [126–128]. Current recommendations include the off-label oral administration of 5 mg 4-aminopyridine three times daily [1, 2, 126] or the off-label oral administration of 10 mg of the sustained release form dalfampridine once or twice daily [1, 2, 127, 128].
Persisting vestibular syndromes
A chronic vestibular syndrome is a combination of symptoms with persistent dizziness lasting months to years and other symptoms such as oscillopsia, nystagmus and gait disturbance. They include persistent postural-perceptual dizziness, bilateral vestibulopathic failure, degenerative, autoimmune or neoplastic diseases, vestibular syndromes with downbeat or upbeat nystagmus, and dizziness due to isolated causes. Examples of the different chronic vestibular syndromes will be provided in the following sections.
Persistent postural-perceptual dizziness
Persistent postural-perceptual dizziness is an umbrella term for known psychosomatic disorders such as secondary somatoform dizziness or phobic positional vertigo. Phobic positional vertigo can be treated with vestibular physiotherapy and cognitive behavioural therapy, possibly combined with antidepressants such as selective serotonin reuptake inhibitors [1, 3], for example citalopram 10–20 mg per day . If selective serotonin reuptake inhibitors are not sufficient, it is also possible to try serotonin norepinephrine reuptake inhibitors [129, 130]. It is necessary to check the serum electrolytes, as many of these antidepressants can be associated with low sodium levels.
Bilateral vestibulopathy is characterised by postural imbalance, gait impairment and, in some patients, oscillopsia . Its major cause is the administration of aminoglycosides such as gentamicin or streptomycin [131, 132]. Aminoglycosides are often used to treat severe infections such as endocarditis. Other causes of bilateral vestibulopathy are chemotherapy with cisplatin [131, 133] and autoimmune inner ear disease, which usually affects both vestibular function and hearing  and may also have ocular manifestations when parts of the peripheral or central nervous system involving the eye are affected. Examples are autoimmune or infectious inflammatory processes, neoplasms, traumas or malformations. Typical ocular effects happen during a probably autoimmune inflammation of the cornea in Cogan’s syndrome [131, 134]. Other pathological mechanisms include bacterial or viral meningitis , bilateral vestibular neuritis [131, 135, 136], bilateral vestibular Schwannomas , bilateral Menière disease [131, 137], neurosyphilis/neurolues [131, 138, 139], neurosarcoidosis [131, 140], congenital malformations  or head trauma [131, 141, 142]. It can be recognised in the emergency department, at the bedside or in the outpatient setting by comparing visual acuity during head rotation with visual acuity when the head is still [131, 143, 144].
The underlying causes of bilateral vestibular loss need to be eliminated or symptomatically treated, for example by stopping aminoglycosides whenever possible. In general, patients should be informed about possible side-effects prior to starting treatment with aminoglycosides, so that they can directly report to the clinician if these symptoms start. If the full picture of vestibulopathy has developed, it mostly persists, because destroyed hair cells in the inner ear do not regenerate  and only the future will show whether molecular gene transfer approaches that work in the mouse model will provide symptom relief in humans . Hence, the best approach is to stop the medication when signs of vestibulopathy first develop, as some hair cells may still be saved this way. In persisting bilateral vestibular loss, the main approach to date is vestibular rehabilitation by means of physiotherapy [16–18, 131, 146]. We recommend that physiotherapy is provided by an expert specialised in vestibular loss.
Degenerative, autoimmune and neoplastic diseases
It is necessary to apply anti-inflammatory treatment for inflammatory lesions and autoimmune diseases , with high-dose glucocorticoid treatment or other immunosuppressive or immune-modulating drugs .
Neurologists should be consulted if there is evidence for an inflammatory lesion. Similarly, these lesions may be caused by tumours or be the result of post-ischaemic events. It is necessary to keep in mind that the symptoms can be the same irrespective of the original cause, with the location of the lesion determining what symptoms the patient may experience [1, 3].
Vestibular syndromes with downbeat or upbeat nystagmus
Dizziness can be associated with vertical forms of nystagmus (downbeat or upbeat nystagmus) [1–3]. Both downbeat and upbeat nystagmus usually coincide with sway vertigo and gait ataxia . They have central aetiologies, such as Arnold-Chiari malformation, cerebellar atrophy and ischaemic or inflammatory lesions in the brainstem or cerebellum, or are idiopathic [1, 147, 148]. Current recommendations include the off-label oral administration of 4-aminopyridine 5–10 mg two to three times daily in both downbeat nystagmus [1–3, 149–151] and upbeat nystagmus [1–3, 152], the oral administration of 3,4-diaminopyridine 10–20 mg two to three times daily [1–3, 153], or the oral administration of clonazepam 0.5 mg three times daily [1, 154–156]. Due to its addictive potential and the impairment of central compensation mechanisms , we do not recommend the administration of clonazepam for more than 3 days. If the symptoms are minor, drug treatment can even be omitted. Downbeat nystagmus will usually improve throughout the day , especially when the head remains in an upright position . According to recent evidence from an observational study, it may be further improved by resting in darkness with the head in an upright position .
There are additional forms of nystagmus that go along with dizziness, but these are less frequent than downbeat or upbeat nystagmus. These less frequent forms of nystagmus, such as acquired pendular nystagmus or periodic alternating nystagmus, are not be summarised here. Detailed recent reviews and therapeutic recommendations can be found elsewhere [1, 2, 156].
Dizziness due to isolated causes
Some cases of dizziness have a clearly defined origin. These include peripheral neuropathy, for example due to deficiency of vitamin B1, B6 or B12 or to diabetes. Recommended therapy is treatment of the vitamin deficiency or better control of diabetes, in addition to physiotherapy and ergotherapy (use of supportive equipment, adapted shoes, etc.). Further isolated causes include ophthalmological disorders, such as a decrease in visual acuity, defects in visual fields or binocular vision, anisometropia, multifocal acuity correction or metamorphopsia and particular forms of cataract . In these cases, it is vital to optimise ophthalmological treatment to reduce the sensation of dizziness. Dizziness following anaemia due to gastrointestinal blood loss requires identification of the cause and specific treatment. A controversial cause of dizziness is cervical vertigo , which could be due to degenerative vertebral processes, trauma  or nerve compression. Treatment options include manual therapy, muscle relaxants or anti-inflammatory medication , specific vestibular rehabilitation [160, 161], stress reduction and anxiety-reducing techniques . More details on the specific treatments are provided elsewhere [160, 161]. If there is a significant nerve compression that cannot be treated conservatively, interventional approaches remain a therapeutic option. Other isolated causes of dizziness include acute infections (which require treatment according to the infectious focus), respiratory diseases associated with hypercapnia, pulmonary embolism, myocardial infarction, or electrolyte imbalance.
This review summarises current treatment recommendations for different forms of dizziness. Optimal treatment strategies should be tailored to the individual patient and underlying aetiology. They should involve multidisciplinary approaches including neurology, ear-nose-throat, ophthalmology, general internal medicine, emergency medicine and neurosurgery, physiotherapy and ergotherapy. In many cases, it is possible to treat the symptoms of dizziness, but not to entirely reverse the underlying pathology, for example in cerebellar stroke or bilateral vestibular loss. Many recommendations are based on retrospective cohort studies (level of evidence 3), case series (level of evidence 4) and expert recommendations or case reports (level of evidence 5), which calls for future prospective studies with higher levels of evidence. Given that dizziness is one of the most frequent reasons why patients consult general practitioners and emergency departments, it is important to pursue future research. This would allow us to make recommendations based on higher levels of evidence. It is particularly important to have comparative studies where different treatment approaches are compared with each other and with placebo. The first steps in this direction have already taken place; for example, there is a multicentre, randomised placebo-controlled trial underway on treatment of vestibular paroxysmia (VESPA) . Hopefully similar trials will be made possible for other causes of dizziness.
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a Division of Internal Medicine, University Hospital, University of Basel, Switzerland
b Emergency Department, University Hospital, University of Basel, Switzerland
c Department of Neurology, University Hospital, University of Basel, Switzerland
d Neurologische Praxisgemeinschaft Bern, Switzerland.
e Department of Otorhinolaryngology, Head and Neck Surgery, Inselspital, University Hospital, University of Bern, Switzerland
f Medical Intensive Care Units, University Hospital, University of Basel, Switzerland
g Department of Neurology, Inselspital, University Hospital, University of Bern, Switzerland
h Department of Neurology and German Centre for Vertigo and Balance Disorders, University of Munich Hospital, Campus Großhadern, Munich, Germany
Shared senior authors: Georgios Mantokoudis, Roland Bingisser, Michael Strupp, Roger Kalla
The authors thank Christian Nickel for his most valuable comments.
The authors Roger Kalla and Georgios Mantokoudis were supported by the Swiss National Science Foundation (Grant #320030_173081). Raoul Sutter received research grants from the Swiss National Foundation (No 320030_169379), the Research Fund of the University of Basel, The Scientific society Basel and the Gottfried Julia Bangerter-Rhyner Foundation.
Raoul Sutter received personal grants from UCB-pharma and Destin Pharma GmbH and holds stocks from Novartis and Roche. Heiko Rust has received travel support from Bayer Healthcare, Teva and Genzyme.
Roger Kalla, MD, Department of Neurology, Inselspital, University Hospital, University of Bern, CH 3010-Bern, roger.kallaat]insel.ch
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