Introduction
Dizziness is an inherently neurologic symptom, even if a systemic cause is primarily responsible. Although dizziness is common to diverse diseases, careful evaluation of dizziness and of any accompanying signs and symptoms can provide the gateway to diagnosis, which in turn is the touchstone of successful treatment.
Vestibular Physiology and Anatomy
Dizziness and the postural instability that often accompanies dizziness typically represent abnormalities of inner-ear function. Vestibular sensation and motor responses are mediated by two relatively simple reflexes: the vestibulo-ocular reflex (VOR) and the vestibulospinal reflex (VSR). VOR maintains visual fixation by generating eye movements to counter head movement in space (e.g., when the head moves upward, the eyes move downward). VSR keeps the head and body upright through changes in axial muscle tone.
Within the vestibular labyrinth in each ear, there are three semicircular canals (SCCs) that respond to angular acceleration of the head in three dimensions [see Figure 1]. When the head turns, the resulting deflection of the cupula in the ampulla of each SCC generates a signal that is transmitted to the brain via the vestibular portion of cranial nerve VIII. The strength of that signal is proportional to the angular velocity of the head. Information about rotation of the head in space reaches the vestibular nuclear complex in the brain stem [see Figure 2], and output from this complex drives the compensatory slow phases of the angular VOR.
The otolith organs (utricle and saccule) respond to linear acceleration during translation of the head (motion in a straight line) and from gravity (uprightness). Linear accelerations cause movement of the gelatinous matrix in the otolithic macula, deflecting the otolith hair cell processes. As these hairs bend, their firing rates change, depending on the direction of acceleration [see Figure 3]. Input from the otoliths drives the responses to head tilt and translation for the compensatory slow phases of the linear VOR.
Transmission of sensory information from the vestibular organs (SCCs and otoliths) occurs through the transduction of physical force into changes in electrical potential by hair cells in the sensory neuroepithelium of each organ.1 Cupular deflection in the SCCs during angular acceleration and otolithic membrane movement within the otolith organs from linear acceleration alter the membrane potential of hair cells, depending on whether the bundle is deflected toward (depolarization) or away (hyper-polarization) from the kinocilium.2 Generator potentials of the hair cells then modulate the firing rate of primary vestibular afferent fibers in cranial nerve VIII. These fibers have a resting spontaneous firing rate and, therefore, are active even when the head is not in motion. Rotation of the head toward any given SCC causes nerves innervating that canal to increase their firing rate; rotation away from a canal causes a decrease in firing in ax-ons from that canal.
The SCCs and the otoliths detect motion in three dimensions to provide information for the VSR, which maintains balance. Visual (optokinetic) and somatosensory pathways also provide partially redundant and complementary signals for balance, enabling recovery in response to vestibular dysfunction. Optokinetic signals supplant labyrinthine signals for the low-frequency sustained components of the VOR to head rotation. These different somatosensory and visual signals that help stabilize posture converge on the same neurons in the vestibular nuclei. Thus, a disturbance in any of the sensory inputs to the vestibular nuclei can lead to a sensory conflict and abnormal vestibular sensations. On occasion, dizziness is produced by visual-vestibular mismatches. A classic example is car sickness: for example, while one reads in the back seat of a moving car, information processed in the visual system informs the brain that the body is not in motion; however, the vestibular system provides information to the contrary. The central neural circuitry of these reflexes is complex. Connections between the vestibular neurons and the oculomotor nuclei form the substrate for the VOR [see Figure 4].
Figure 1 Soft tissue structures within the bony labyrinth.
Figure 2 (a) Shown is the functional organization of the cupula and the associated hair cells within the ampulla of the semicircular canals. The cupula changes position depending on the direction of angular acceleration. (b) The relation between the hair cell stereocilia and kinocilium is also shown. Movement of the stereocilia (cupula displacement) in a direction toward the kinocilium results in depolarization of hair cell axons, which project through cranial nerve VIII into the brain stem vestibular pathways. Movement of stereocilia in the opposite direction results in hyperpolarization. Similar anatomic arrangements are seen in the saccule and utricle. (c) The location of the semicircular canals in the head is shown. In the lateral semicircular canals, the kinocilium is located on the side nearest the utricle, whereas in the superior and posterior semicircular canals, the kinocilium is away from the utricle.
For the VSR, the SCCs contribute to postural reflexes via projections to the lateral vestibular nucleus, giving rise to the lateral vestibulospinal tract. The vestibular contribution to sensations of head and body motion and spatial position likely reaches consciousness through the rostral projections of vestibular nuclei to the cerebellum, thalamus, and cerebral cortex.
Clinical Manifestations of Vestibular Dysfunction
Vestibular dysfunction can present in a variety of ways, including oscillopsia (the visual illusion of environmental movement), postural instability, and spatial disorientation. Patients often describe difficulty driving, walking in large open spaces, or walking in crowded environments such as shopping malls and supermarkets. They will avoid head movement. Sensory-rich environments provoke and intensify sensory conflicts, which can produce feelings of disorientation and vegetative symptoms such as nausea and vomiting.3
On examination, patients complaining of vertigo may exhibit nystagmus, as a result of abnormalities in the VOR. Vestibu-lar nystagmus has a slow phase, in which the eyes drift during attempted steady fixation, followed by a fast (or quick) phase, in which the eyes reset on the fixation target through rapid eye movements similar to saccades (the eye movements normally made from place to place with the head still or while reading). Nystagmus may be spontaneous or induced by changes in gaze or body position; the distinction between spontaneous and induced nystagmus, as well as the direction of the nystagmus (i.e., horizontal, torsional, or vertical), has considerable diagnostic utility [see Tables 1 and 2]. By convention, nystagmus is named by the direction of the quick phase.
Vestibular signs and symptoms may occur when the head is still, when the head moves, or both. Static disturbances suggest a different set of diagnostic possibilities than dynamic disturbances.
Static imbalance
Vestibular disturbance in the absence of head motion is characterized by vertigo and spontaneous nystagmus, which results when a unilateral lesion disturbs the normal balance of tonic discharges from the two labyrinths. Other clinical features of static vestibular disturbance include diplopia (double vision); tilt of the head and body; and vegetative symptoms such as nausea, vomiting, diaphoresis, and occasionally hypotension and syncope.
Skew deviation, a vertical misalignment of the eyes, is the hallmark of an imbalance in the tonic levels of activity underlying otolith-ocular reflexes. Patients with this misalignment often complain of vertical diplopia, sometimes with the illusion of tilt of the visual world, and the head may also be tilted. Skew deviation can be detected clinically by using an ocular cover test. In this test, the physician moves a cover from one of the patient’s eyes to the other while watching for vertical corrective eye movement when the cover is switched.
Skew deviation, ocular counterrolling (rotation of the eyes about the line of sight; ocular torsion), and head tilt together constitute the ocular tilt reaction.4 The ocular tilt reaction can occur with lesions anywhere in the otolith-ocular pathway; this pathway includes the peripheral labyrinth,5 vestibular nerve, vestibular nucleus in the medulla, medial longitudinal fasciculus in the pons or midbrain, and interstitial nucleus of Cajal [see Figure 4]. With peripheral and vestibular nucleus lesions (e.g., vestibular nerve section or Wallenberg syndrome), the lower eye is on the side of the lesion. With lesions above the level of otolith-ocular pathway decussation at the vestibular nucleus (e.g., an internuclear ophthalmoplegia from a lesion in the medial longitudinal fasciculus in the pons or midbrain), the higher eye is on the side of the lesion and the head is tilted toward the lower eye.6
Abnormalities in the VSR are assessed with the tandem walking test: the patient places one foot directly in front of the other while keeping the head relatively fixed; the test is done first with the eyes open and then with the eyes closed. Problems with tandem walking suggest an imbalance in vestibular tone—patients will generally veer or fall toward the paretic side.
Static imbalance should also be assessed with the Romberg test, in which the patient stands with feet together and closes the eyes while holding the arms and hands outward with palms up. Excessive sway on the Romberg test can indicate abnormalities in otolith-spinal reflexes.
Past-pointing of the arms or feet to previously seen targets with eyes closed may be another sign of vestibulospinal imbalance. For the arms, past-pointing is best elicited by having the patient repetitively raise both arms over the head, with the index fingers extended, and then bring them down, with eyes closed, toward the examiner’s index fingers located at waist level. Errors in pointing generally are in the direction of the weak labyrinth and should be equal in the two arms.
In some cases, the characteristics of spontaneous nystagmus can help localize the lesion. When vestibular damage is peripheral, the nystagmus is characteristically diminished by visual fixation and increased when fixation is eliminated; thus, it is best observed by techniques that impair or remove visual fixation (e.g., occlusive ophthalmoscopy, Frenzel glasses).7 The slow phases of spontaneous nystagmus generally move toward the side of a peripheral vestibular lesion. For example, in the case of a left vestibular neuritis, right vestibular function is relatively increased; consequently, in such cases, patients exhibit slow eye movements to the left, toward the neuritis, with a corresponding fast phase to the other side (right-beating nystagmus).
Nystagmus with a slow phase toward the side of the lesion is also seen with unilateral lesions in the cranial nerve VIII entry zone or the vestibular nucleus. As with plaques of demyelina-tion from multiple sclerosis (MS), a lesion in the last few millimeters of cranial nerve VIII before it enters the brain stem at the pontomedullary junction can be indistinguishable from a process affecting the peripheral labyrinth. However, oscillopsia associated with a peripheral vestibular lesion often resolves quickly as compensatory mechanisms come into play; in contrast, compensation for oscillopsia caused by a brain stem disorder generally does not occur rapidly or to the same extent.
Figure 3 (a) The otolith organs (the utricle and saccule) are specially adapted to detect linear accelerations, including those in the gravitational plane. (b) Otolith hair cell stereocilia and kinocilia project into a gelatinous membrane that is covered by crystalline particles of calcium carbonate called otoconia. (c) Shearing forces imposed across the membrane occur with static tilt and result in characteristic changes in the movement of stereocilia that can produce either depolarization or hyperpolarization, depending on the direction of movement.
Figure 4 Shown are the excitatory neural connections that give rise to the three-dimensional vestibular ocular reflex. (left) Primary afferents innervating the anterior semicircular canal (AC) synapse onto second order neurons in the vestibular nuclei. Projections cross and ascend in the medial longitudinal fasciculus (MLF) to the contralateral third cranial nerve (oculomotor) nucleus, specifically the inferior oblique (IO) and superior rectus (SR) subnuclei. These motor neurons innervate the inferior oblique muscle on the side opposite the stimulated AC and the ipsilateral superior rectus (via a second decussation) muscle to move the eyes in a vertical upward and torsional direction (upper poles away from the stimulated canal). (center) Posterior canal (PC) afferents project centrally to synapse in the vestibular nucleus before decussating and traveling in the MLF to innervate the contralateral third and fourth (trochlear) cranial nerve nuclei. Motor neurons ultimately contact the inferior rectus muscle (IR) on the side opposite the stimulated PC and the ipsilateral superior oblique muscle (via a second decussation). (right) Afferent input from the horizontal canal (HC) system projects to the medial vestibular (MV) nucleus and then crosses to innervate two populations of cells in the contralateral abducens (VI) nucleus: motor neurons project to the lateral rectus (LR) muscle, and interneurons cross back over and travel in the MLF to innervate the medial rectus (MR) subnucleus of cranial nerve III, which innervates the ipsilateral MR muscle. (LV—lateral vestibular nucleus; PH—prepositus nucleus hypoglossi; SO—superior oblique muscle; SV—superior vestibular nucleus; III—oculomotor nuclear complex; IV—trochlear nucleus; V—inferior vestibular nucleus; VI—abducens nucleus; XII—hypoglossal nucleus)
Other central abnormalities are less localizable by the direction of nystagmus. With vestibular cerebellar lesions, the slow phase is typically to the side opposite the lesion—likely because of removal of cerebellar inhibition of the ipsilateral vestibular apparatus. Pure upbeat, pure downbeat, or pure torsional nystagmus almost always has a central origin. A mixed horizontal-tor-sional or vertical-torsional nystagmus, however, usually indicates a peripheral lesion involving the entire vestibular nerve or all three SCCs in one labyrinth [see Nystagmus, below].
Gaze-evoked nystagmus commonly occurs as a side effect of certain medications—especially anticonvulsants, hypnotics, and tranquilizers—and with disease of the vestibulocerebellum or its brain stem connections in the medial vestibular nucleus and the nucleus prepositus hypoglossi (both are components of the neural integrator, along with the cerebellar flocculus).8 It is not present in straight-ahead gaze but is elicited when patients attempt to hold the eyes eccentric in the orbit. The eyes will drift back toward the center, and then a quick phase will follow to move the eyes back into the desired position. When gaze-evoked nystagmus results from toxic or metabolic conditions (e.g., Wer-nicke encephalopathy, alcohol intoxication), it is direction chang-ing—left beating in left gaze, right beating in right gaze. This distinguishes it from nystagmus caused by labyrinthine weakness, which is always direction fixed.
Dynamicimbalance
Dynamic vestibular disturbances are provoked by head motion or change in position. They may reflect unilateral or bilateral abnormalities in amplitude, direction, or timing of the VOR and VSR; or they may reflect mechanical disruptions in the labyrinth (e.g., benign paroxysmal positioning vertigo [BPPV]). Unilateral lesions sometimes cause dynamic disturbances through loss of the normal push-pull relation, whereby activity from one labyrinth increases as that from the other decreases, which results in compensatory eye movement in response to head motion. Bilateral vestibular lesions (e.g., from aminoglycoside toxicity) lead to dynamic disturbances because of an overall loss of function but rarely give rise to vegetative symptoms. Dynamic vestibulospinal function can be clinically assessed by observing postural stability while the patient makes rapid turns during ambulation.
In the case of a dynamic imbalance or bilateral vestibular weakness, angular VOR can be tested clinically by observing the effects of head rotation on visual acuity and on eye movements themselves [see Table 3]. For example, dynamic visual acuity is evaluated using a near vision card at 14 in. or a distance acuity chart; the patient’s head is passively rotated—horizontally (as in shaking the head, "no"), then vertically ("yes"). The amplitude of the movement is not critical, but the head should pass through the straight-ahead position twice each second. Patients with impaired labyrinthine function usually lose more than two lines of acuity secondary to a reduced VOR gain (eye velocity/head velocity).
Table 1 Nystagmus and Its Likely Causes
|
Type of Nystagmus |
Likely Cause |
Comments |
|
Purely torsional |
Brain stem disease at vestibular nuclei |
Nystagmus from unilateral peripheral vestibular loss can appear purely torsional because of suppression of the horizontal component |
|
Purely vertical Downbeat in primary position Upbeat in primary position |
Diverse intrinsic brain stem abnormalities; craniocervical junction (Arnold-Chiari malformation, cerebellar lesion), pontomedullary junction, or pontomesencephalic junction lesion |
Often increases in intensity in lateral gaze |
|
Horizontal-torsional |
Labyrinthine dysfunction; lesions within cranial nerve VIII or the vestibular nucleus |
Horizontal component may be suppressed with vision, causing a peripheral nystagmus to appear purely torsional if viewed with fixation present |
|
Purely horizontal Periodic alternating (jerk, changes direction every 2 min) |
Lesion in the cerebellar nodulus |
Majority of cases can be treated successfully with baclofen |
|
Primarily horizontal Even during attempted up or down gaze, accented by attempted fixation, diminished by convergence or active eyelid closure, associated with a head turn, sometimes accompanied by reverse (or perverted) smooth pursuit |
Congenital |
Many patients with congenital nystagmus exhibit normal visual acuity; in one form, latent (occlusion) nystagmus, the slow-phase direction depends on which eye is viewing |
|
Pendular (sinusoidal oscillation rather than unidirectional drift) |
Congenital |
Nystagmus often appears superficially pendular, but pendular nystagmus may be a sequel to brain stem stroke or a manifestation of various disorders, including multiple sclerosis, Whipple disease, toluene intoxication, acquired visual loss, and Pelzius-Mertzbacher disease |
|
Convergent retraction |
Midbrain lesion |
Usually coexists with upgaze paralysis (Parinaud syndrome) |
|
Seesaw (one eye ascends and intorts; the other descends and extorts) |
Midbrain lesion |
— |
|
Dissociated, or disconjugate (greatest or only present in abducting eye) |
Internuclear ophthalmoplegia |
— |
Corrective saccades during head rotations are also a sign of an abnormal VOR. To assess the VOR clinically, the patient is requested to maintain gaze on the examiner’s nose. For yaw (horizontal) and pitch (vertical) rotations, the examiner oscillates the patient’s head at a rate of about once every 2 seconds, turning the head across almost the entire ocular motor range [see Table 1]. The patient is instructed to continue looking carefully at the examiner’s nose and to avoid blinking. During this maneuver, patients can maintain gaze on the target using both the VOR and pursuit eye movements. As the speed of head movements increases, the appearance of any saccadic, rather than slow, eye movements indicates a deficit in the VOR, usually from a peripheral vestibular paresis on the side toward which the head is turning when the rapid eye movements are required. Brief high-acceleration head thrusts are then per-formed,11 starting with the head turned about 15° from center and ending with the head facing directly forward.12 If a corrective (catch-up) saccade is required to move the eyes back onto the target after the rapid head turn, then a canal paresis is present on the side toward which the head had just been turned.
Head-shaking nystagmus is elicited by turning the patient’s head vigorously side to side, with the chin pitched slightly downward and the eyes closed, about 20 to 30 times.13 Any nystagmus present after head rotation stops and eyes are opened is noted; this finding is best assessed using Frenzel glasses so that vision is occluded. Normal individuals show at most a beat or two, whereas a peripheral lesion causing a unilateral loss of labyrinthine function usually produces vigorous nystagmus after head shaking; the slow phases are initially directed toward the side of the lesion, and the fast phases are directed away.14 Cerebellar dysfunction and other central disturbances may also lead to nystagmus after horizontal head shaking, but generally, the nystagmus is most often vertical (so-called cross-coupled nystagmus).15 Nystagmus after head shaking can arise from mechanical disturbances in the labyrinth as well (e.g., perilymph fistula, Meniere disease, or abnormality of the cupula).
