Congenital or acquired retinal disorders causing blindness, such as Leber congenital amaurosis, lead to continuous jerk nystagmus with components in all three planes and that changes direction over the course of seconds or minutes. This nystagmus is associated with a drifting “null point”—the eye position at which nystagmus changes direction—that probably reflects inability to calibrate the ocular motor system. This type of nystagmus often shows an increasing-velocity waveform (Fig. 21.1C). Recent developments in gene therapy for retinal disorders suggest that if vision can be restored, this type of nystagmus will be suppressed.

Optic nerve disease is commonly associated with pendular nystagmus. With unilateral disease of the optic nerve, nystagmus largely affects the abnormal eye, resulting in monocular or markedly asymmetric nystagmus. When both optic nerves are affected, the amplitude of nystagmus is often greater in the eye with poorer vision (the Heimann–Bielschowsky phenomenon). This phenomenon also occurs in patients with profound amblyopia, dense cataract, and high myopia (Video 21.1). Oscillations may disappear when vision is restored, supporting the contention that in such cases, the ocular oscillations are caused by loss of vision rather than by any primary disorder of the ocular motor system.

Parasellar lesions such as pituitary tumors have traditionally, albeit rarely, been associated with seesaw nystagmus (see below). Seesaw nystagmus also occurs in persons whose optic nerve axons do not cross in the optic chiasm, such as some patients with severe albinism. Thus, it is possible that visual inputs, especially crossed inputs, are important for optimizing vertical–torsional eye movements and if interrupted, lead to seesaw oscillations.

Horizontal nystagmus is a documented finding in patients with unilateral disease of the cerebral hemispheres, especially when the lesion is large and posterior. Such patients show a constant-velocity drift of the eyes toward the intact hemisphere (i.e., quick phases directed toward the side of the lesion, which is often low amplitude) and also usually show asymmetry of horizontal smooth pursuit that can be brought out using an optokinetic tape or drum. The response is reduced when the stripes move, or the drum is rotated, toward the side of the lesion. Whether this asymmetry occurs primarily
from impairment of parietal cortex necessary for directing visual attention or from disruption of cortical areas important for processing motion vision is unclear.

Acquired pendular nystagmus is a common feature of acquired and congenital disorders of central
myelin, such as multiple sclerosis (MS), toluene abuse, Pelizaeus–Merzbacher disease, and peroxisomal disorders. Because optic neuritis often coexists in patients with MS who have pendular nystagmus, prolonged response time of the visual processing might be responsible for the ocular oscillations. However, the nystagmus often remains unchanged in darkness, when visual inputs should have no influence on eye movements. A more likely possibility is that visual projections to the cerebellum are impaired, leading to instability in the reciprocal connections between brainstem nuclei and cerebellum that are important for recalibration.

Acquired pendular nystagmus may be one component of the syndrome of oculopalatal (pharyngo-laryngo-diaphragmatic) myoclonus. This condition usually develops several months after brainstem or cerebellar infarction, although it may not be recognized until years later. Oculopalatal myoclonus also occurs with degenerative conditions. The term “myoclonus” is misleading because the movements of affected muscles are to-and-fro and are approximately synchronized, typically at a rate of about 2 cycles per second. The palatal movements thus may be termed “tremor” rather than myoclonus, and the eye movements are really a form of pendular nystagmus. Although the palate is most often affected, movements of the eyes, facial muscles, pharynx, tongue, larynx, diaphragm, mouth of the eustachian tube, neck, trunk, and extremities may occur.

The ocular movements typically consist of to-and-fro oscillations. They often have a large vertical component, although they may also have small horizontal or torsional components. The movements may be somewhat disconjugate (both horizontally and vertically), with some orbital position dependency, and some patients show cyclovergence (torsional vergence) oscillations. Occasionally, patients develop the eye oscillations without movements of the palate, especially following brainstem infarction. Eyelid closure may bring out the vertical ocular oscillations. The nystagmus sometimes disappears with sleep, but the palatal movements usually persist. The condition is usually intractable, and spontaneous remission is uncommon.

The main pathologic finding with palatal myoclonus is hypertrophy of the inferior olivary nucleus (Fig. 21.3A), which may be seen using magnetic resonance (MR) imaging (Fig. 21.3B and C). There may also be destruction of the contralateral dentate nucleus. Histologically, the olivary nucleus has enlarged, vacuolated neurons with enlarged astrocytes. It has been postulated that the nystagmus of oculopalatal tremor results from instability in the projection from the inferior olive
to the cerebellar flocculus, a structure thought to be important in the adaptive control of the VOR.

Vergence pendular oscillations occur in patients with MS, brainstem stroke, and cerebral Whipple disease. In Whipple disease, the oscillations typically have a frequency of about 1.0 Hz and are accompanied by concurrent contractions of the masticatory muscles, a phenomenon called oculomasticatory myorhythmia (Video 21.3). Supranuclear paralysis of vertical gaze also occurs in this setting and is similar to that encountered in progressive supranuclear palsy.

At least two possible explanations have been offered to account for the convergent-divergent nature of vergence pendular oscillations: A phase shift between the eyes, produced by dysfunction in the normal yoking mechanisms, or an oscillation affecting the vergence system itself. The latter explanation is more likely because patients who have been studied show no phase shift (i.e., are conjugate) vertically, and because the relationship between the horizontal and torsional components is similar to that occurring during normal vergence movements (excyclovergence with horizontal convergence).

Disease affecting the peripheral vestibular pathway (i.e., the labyrinth, vestibular nerve, and its root entry zone) causes nystagmus with linear slow phases (Fig. 21.1A). Such unidirectional slow-phase drifts reflect an imbalance in the level of tonic neural activity in the vestibular nuclei. If disease leads to reduced activity, for example, in the vestibular nuclei on the left side, then the vestibular nuclei on the right side will drive the eyes in a slow phase to the left. In this example, quick phases will be directed to the right—away from the side of the lesion. Two features of the nystagmus itself are useful in identifying the vestibular periphery as the culprit: Its trajectory (direction) and whether it is suppressed by visual fixation.

The trajectory of nystagmus can often be related to the geometric relationships of the semicircular canals and to the finding that experimental stimulation of an individual canal produces nystagmus in the plane of that canal. Thus, complete unilateral labyrinthine destruction leads to a mixed horizontal–torsional nystagmus (the sum of canal directions from one ear), whereas in benign paroxysmal positional vertigo (BPPV), a mixed upbeat–torsional nystagmus reflects posterior semicircular canal stimulation. Pure vertical or pure torsional nystagmus almost never occurs with peripheral vestibular disease because this would require selective lesions of individual canals from one or both ears, an unlikely event.

Nystagmus caused by disease of the vestibular periphery often is more prominent, or may only become apparent, when visual fixation is prevented. The reason for this is that when visually generated eye movements are working normally, as they usually are in patients with peripheral vestibular disease, they will slow or stop the eyes from drifting.

Another common, but not specific, feature of nystagmus caused by peripheral vestibular disease is that its intensity increases when the eyes are turned in the direction of the quick phase—Alexander’s law. This probably reflects an adaptive strategy developed to counteract the drift of the vestibular nystagmus and so establish an orbital position (i.e., in the direction of the slow phases) in which the eyes are quiet and vision is clear. This phenomenon forms the basis for a common classification of unidirectional nystagmus. Nystagmus is called “first degree” if it is present only on looking in the direction of the quick phases, “second degree” if it is also present in the central position, and “third degree” if it is present on looking in all directions of gaze.

Although these clinical features help make the diagnosis of peripheral vestibular disease, it is important to realize that brainstem and cerebellar disorders may sometimes mimic peripheral disease and, especially in elderly patients or those with risk factors for vascular disease, careful observation is the prudent course.

Vestibular nystagmus is often influenced by changes in head position. This feature can be used to aid in diagnosis, especially of BPPV. Patients with BPPV complain of brief episodes of vertigo precipitated by change of head position, such as when they turn over in bed or look up to a high shelf. The condition may follow head injury or viral neurolabyrinthitis.

To test for nystagmus and vertigo in a patient with possible BPPV, the examiner should place the patient supine and turn the head toward one shoulder and then quickly move the head and neck together into a
head-hanging (down 30 to 45 degrees) position. About 2 to 5 seconds after the affected ear is moved to this dependent position, a patient with BPPV will report the onset of vertigo, and a mixed upbeat–torsional nystagmus, best viewed with Frenzel goggles, will develop. The direction of the nystagmus changes with the direction of gaze. Upon looking toward the dependent ear, it becomes more torsional; on looking toward the higher ear, it becomes more vertical. This pattern of nystagmus corresponds closely to stimulation of the posterior semicircular canal of the dependent ear (which causes slow phases mainly by activating the ipsilateral superior oblique and contralateral inferior rectus muscles). The nystagmus increases for up to 10 seconds, but it then fatigues and is usually gone by 40 seconds. When the patient sits back up, a similar but milder recurrence of these symptoms occurs, with the nystagmus being directed opposite to the initial nystagmus. Repeating this procedure several times will decrease the symptoms and make the signs more difficult to elicit. This habituation of the response is of diagnostic value because a clinical picture similar to that of BPPV can be caused by cerebellar tumors, MS, or posterior circulation infarction. With such central processes, however, there is no latency to onset of nystagmus and no habituation of the response with repetitive testing.

Otolithic debris in the respective canals (canalolithiasis) interferes with the flow of endolymph or movement of the cupula and is probably responsible for BPPV. Neck movement causing vertebrobasilar kinking and vertigo as an isolated manifestation of transient brainstem ischemia is an uncommon mechanism; in such cases, associated neurologic symptoms are usually present.