The modern paradigm for the clinical management of dizziness and vertigo was introduced by Drachman and Hart in a seminal 1972 publication [1]. Based on patient response to the question "What do you mean by 'dizzy?'," dizziness was classified into one of four types that best reflected the subjective descriptions of the symptoms [2,3]:

The labyrinth in each inner ear houses the systems that serve the functions of hearing (auditory) and balance (vestibular). The auditory system involves the cochlea, which transmits sound signals to the brainstem via the cochlear branch of the 8th cranial nerve. The vestibular system is comprised of the vestibular end-organs in the labyrinth, the vestibular nuclei in the brainstem and cerebellum, and the vestibular branch of the 8th nerve, which relays labyrinthine input to the vestibular nuclei. The 8th cranial nerve is also called the vestibulo-cochlear nerve [10,11,12].

Within each labyrinth are five vestibular end-organs (three semicircular canals and two otolith organs) that help maintain spatial orientation, postural control, and egocentric perception. Changes in angular and linear head acceleration, movement, and orientation to gravity are detected and signaled via the 8th nerve to brainstem and cerebellar circuits, through thalamic and spinal vestibular projections, and finally to the cerebral cortex [13,14,15].

Vertigo, dizziness, spatial disorientation, and disequilibrium can result from: asymmetrical vestibular inputs; vestibular hypofunction causing sensory mismatch in brain integration of sensory inputs; pathologies that affect any peripheral (e.g., inner ear, 8th cranial nerve) or central (e.g., vestibular nuclei and brainstem or cerebellar connections) vestibular system component; or a host of systemic, drug-effect, psychiatric, and physical trauma-related factors [14,16,17]. Around 80% of dizziness or vertigo cases are peripheral and 20% are central in origin [11].

Vestibular neuritis, the second most common cause of vertigo (after BPPV), is a viral or post-viral inflammatory disorder affecting the vestibular portion of the 8th cranial nerve. It most commonly affects persons 30 to 50 years of age, and men and women are equally affected. New cases are more common in the spring and early summer [10,34]. Histopathologic nerve studies of these patients are consistent with a viral inflammatory etiology [15].

Vestibular neuritis is characterized by the sudden, acute onset of severe vertigo, nausea, vomiting, and gait instability without hearing loss, typically preceded by an upper respiratory tract infection [35]. The course and treatment of vestibular neuritis and viral labyrinthitis are similar; in both, the severity of acute vestibular symptoms can raise concerns of a central etiology, and the severity of vertigo, nausea, and vomiting reflects the severity of vestibular asymmetry [7,15,34].

Profound hearing loss, severe vertigo, ataxia, and nausea and vomiting are common symptoms of bacterial labyrinthitis. Suppurative labyrinthitis almost always results in permanent, profound unilateral hearing loss (or bilateral loss with meningitis). Serous labyrinthitis results in unilateral, high-frequency hearing loss in the affected ear. Regardless of etiology, bacterial labyrinthitis accounts for 35% of all adult-onset cases of hearing loss [35].

Vestibular paroxysmia is characterized by recurrent spontaneous vertigo attacks that are brief (several seconds up to one minute), and frequent (up to 30 per day) [44]. In one study, vestibular paroxysmia accounted for 3.7% of 17,718 consecutive outpatients in a multidisciplinary vertigo and balance disorders center. Men are affected twice as often as women, and the bimodal age of onset peaks in early childhood and again between 40 and 70 years of age [45].

Vestibular migraine is the most common central cause of recurrent spontaneous attacks of vertigo. "Vestibular migraine" is the preferred name for this disorder, because patients may experience a range of vestibular symptoms not limited to vertigo (e.g., dizziness, nausea, vomiting) [18,48].

Anxiety can impair ocular motor reflexes and gaze control, which may contribute to visual and visual-vestibular syndromes. Anxious states can amplify a normative gaze bias toward potentially threatening stimuli in the visual field, which, in patients with social anxiety disorder, may drive hypervigilance-avoidance gaze patterns. The impairing effect of anxiety on gaze control reduces gaze stability on visual targets, which may underlie dizziness and visual symptoms in PPPD [74,75].

Aminoglycosides are the most vestibulotoxic of all ototoxic drugs. The introduction of streptomycin in 1944 for treatment of tuberculosis brought ototoxicity to clinical attention, as a substantial number of treated patients developed irreversible cochleo-vestibular dysfunction [98,99].

Accurate diagnosis is an essential precondition for effective treatment of dizziness and vertigo, best ensured by defining the rapidity of onset, the context, associated symptoms, intermittent or persistent nature of dizziness, and triggers of intermittent symptoms during patient history-taking. This is called the "timing and triggers" diagnostic workup. The workup is structured using the algorithm Triage-TiTrATE-Test [8,36,102]:

Almost all patients with vertigo feel worse with head movements. The critical distinction is whether head movements trigger (symptoms appear only when provoked by movements) or exacerbate (movements worsen pre-movement vertigo) symptoms [8,19].

HINTS is an acronym for three ocular motor tests—the head impulse test (HIT), gaze testing for nystagmus, and alternate cover test for skew deviation—that are combined to differentiate central from peripheral causes of dizziness. Nystagmus is a key observed response. Normal visual fixation can suppress mild nystagmus, but Frenzel lenses worn by the patient block visual fixation and magnify examiner view of eye movements [8,10,19]. When conducting the HIT, have the patient fixate his/her gaze on a midline target (e.g., the examiner's nose), then rapidly rotate his/her head 20 degrees to the right or left, bring head back to midline, then rotate to the other side. The presence of a corrective saccade is "positive" for abnormal vestibulo-ocular reflex, which generally indicates a peripheral vestibular process. Gaze that remains locked on the midline target is normal. A normal HIT in patients with AVS is highly suspicious for stroke, but HIT is only useful in patients with AVS and nystagmus. In patients with dizziness (with urosepsis or dehydration) without nystagmus, a normal HIT is a misleading false-positive for stroke.

As mentioned, clinicians should distinguish triggers from exacerbating features [36]. Prototype t-EVS causes are BPPV and orthostatic hypotension; less commonly, it is caused by superior canal dehiscence syndrome [8]. Possible dangerous causes include central paroxysmal positional vertigo and serious causes of orthostatic hypotension, such as internal bleeding. Patients with panic or anxiety disorders may also complain of episodic vertigo, lightheadedness, or dizziness during panic attacks that are triggered or spontaneous. Studies show a high prevalence of vestibular dysfunction for these patients [113].

Episodic positional symptoms are common to all causes of t-EVS, differentiated by targeted history and exams. BPPV is identified by maneuvers that reproduce dizziness combined with an observed pattern of nystagmus. Orthostatic hypotension is diagnosed by observing a significant fall in blood pressure upon sitting and standing. Dangerous t-EVS mimics are identified by careful attention to the corresponding signs and symptoms that differentiate these benign conditions from potentially more serious disorders [36]. Positional triggers, such as rolling over in bed or reclining, are common in BPPV but should not occur in orthostatic hypotension [8]. Unlike head position changes in BPPV, the vertigo and oscillopsia attacks in superior canal dehiscence syndrome are triggered by pressure-related changes of the external auditory canals (e.g., loud sounds, Valsalva maneuver) [21].

The nystagmus characteristics of BPPV and central paroxysmal positional vertigo are distinct. Atypical nystagmus (downbeat or horizontal) is suggestive of central paroxysmal positional vertigo, and pure vertical (up- or downbeating) nystagmus should be considered of central origin until proven otherwise [8,22]. Central mimics of BPPV less often involve strokes and more often involve posterior fossa neoplasm, hemorrhage, or demyelination recognized by association with other abnormalities [105,114].

Central paroxysmal positional vertigo also includes common, benign causes, such as alcohol or sedative intoxication. Such patients are more apt to complain of continuous, persistent dizziness exacerbated (not triggered) by position change, often readily diagnosed based on context and other signs of intoxication [8,36].

Drug classes and agents commonly used as vestibular suppressants include antihistamines, benzodiazepines, scopolamine, dopamine antagonists, and ondansetron (Table 2). Antihistamines (e.g., meclizine, diphenhydramine, dimenhydrinate) block the release of histamine and acetylcholine and are especially beneficial in vestibular-mediated nausea, vomiting, and motion sickness. Side effects include sedation, confusion, dry mouth, and urinary retention. Meclizine is preferred because it has minimal anticholinergic effects, causes less sedation, and is effective in the treatment of vertigo due to labyrinth dysfunction. It is also the drug of choice in pregnancy [124]. Diphenhydramine is recommended for the treatment of Ménière disease [127].

In peripheral vestibular disorders, all vestibular suppressants can interfere with central compensation, and their use is recommended to not exceed three days [15,21,128]. The goal is for patients to rapidly receive specialist care, but patients may not get an immediate appointment and remain highly symptomatic. In this context, vestibular suppressants should continue for symptom control until optimized treatment is initiated by a specialist [120].

Strategic substitution exercises promote the use of sensory stimuli and spatial cues from vision and proprioception to substitute for loss of vestibular inputs. Cervico-ocular reflex input is strengthened to reduce spatial uncertainty, and alternative spatial cues can improve balance and walking [43,135,136].

Canalith repositioning procedures (CRPs) are the first-line therapy option and the most effective treatment for BPPV for patients with prolonged symptoms and/or frequent recurrences. Vestibular suppressants are generally avoided, though a brief course of an antihistamine (e.g., meclizine) may be indicated for initial symptom control. This may be all that is needed for patients with mild, self-limited symptoms and infrequent recurrences. Rarely, BPPV can be refractory to CRPs and require surgical occlusion of the affected semicircular canal [15].

CRP is strongly recommended as initial therapy for pc-BPPV [21]. It has a demonstrated high success rate in improving vertigo and in restoring gait and balance in persons with pc-BPPV [143]. The Epley maneuver is the preferred CRP for pc-BPPV and has more than 20 years of evidential support. Meta-analyses have found that, compared with sham or control groups, the Epley led to significantly greater rates of complete vertigo resolution and conversion from a positive to a negative Dix-Hallpike. After 12 months, the Epley was superior to sham maneuver in conversion to negative Dix-Hallpike and perceived disability [21,144].

With vestibular paroxysmia, the characteristic brevity (seconds up to a few minutes, very seldom many hours) and frequency of recurring vertigo attacks makes the differential diagnosis generally straightforward [45]. The frequent vertigo attacks respond to carbamazepine (200–800 mg/day) or oxcarbazepine (300–900 mg/day), even in the lower dose range. Both drugs are recommended to start with a low dose, slowly progressing to higher doses as necessary [120].

During 2001–2004, an estimated 35.4% of adult Americans had vestibular dysfunction requiring medical attention. The prevalence of balance impairment and vestibular dysfunction increases with age—the rate is 75% among persons older than 70 years and 85% among persons 80 years of age or older. Persons with vestibular disorders have an eight-fold increase in risk of falling and resultant morbidity/mortality. Uncompensated vestibular hypofunction results in postural instability, visual blurring with head movement, and subjective complaints of dizziness and/or imbalance [43].