cerebellar disease.
Vestibular Nystagmus
Peripheral Vestibular Nystagmus
Patients with peripheral vestibular nystagmus typically present with a sudden, sometimes dramatic, onset of dysequilibrium with vertigo, nausea, and vomiting (Table 9-1). Patients often recognize that their symptoms are worsened by particular head movements or postures. Oscillopsia, tinnitus, and hearing loss may also occur. After the acute phase of peripheral vestibular loss, which typically lasts days, patients experience a slow period (lasting weeks to months) of gradually waning symptoms. Even patients who become asymptomatic may experience discomfort months to years later when their vestibular system is challenged, as when riding in a fast-moving car or boat.
Table 9-1
Peripheral vestibular nystagmus arises from end-organ (eg, semicircular canals, otolithic structures, vestibular nerve) dysfunction. End-organ damage is usually unilateral or asymmetric (except in cases of toxicity) and disrupts the normally symmetric vestibular afferent inputs to the neural integrator. Because the output of the neural integrator is routed to the contralateral paramedian pontine reticular formation, loss of tonic symmetry produces a directional bias toward the diseased side. A reduction in input from a left-sided vestibular lesion, for instance, results in a leftward bias and requires a corrective saccade away from the side of the lesion. Thus, a left-sided lesion would produce leftward slow phases and right jerk nystagmus.
Peripheral vestibular nystagmus related to vestibular neuropathy typically disrupts output from all 3 semicircular canals and the otolithic organs, producing a mixed horizontal-torsional pattern of nystagmus that changes depending on the direction of gaze. This follows Alexander’s law: the nystagmus is more pronounced when gaze is directed toward the side of the fast-beating component. Depending on the severity of the lesion, the nystagmus may be evident in primary position. A skew deviation also may be present (see Chapter 8). A purely vertical or torsional nystagmus almost always signifies a central lesion (discussed in the following section).
A characteristic feature of peripheral vestibular nystagmus is the ability of visual fixation to dampen the nystagmus. The effect of visual fixation on nystagmus can be evaluated during direct ophthalmoscopy by temporarily covering the contralateral fixating eye. Other methods for enhancing vestibular nystagmus include vigorous head shaking, hyperventilation, mastoid vibration, and the Valsalva maneuver.
Peripheral vestibular dysfunction, often accompanied by nystagmus, usually occurs in 1 of 4 clinical patterns. The first is an acute, monophasic disorder that occurs secondary to a (presumed viral) vestibular neuronitis. The second is a recurrent form of vestibular dysfunction that is usually
associated with auditory symptoms (eg, tinnitus and hearing loss). This disorder, exemplified by Ménière disease, is usually progressive, although there may be long symptom-free intervals. The third clinical pattern is a paroxysmal dysfunction of the vestibular system that produces vertigo in response to certain postures of the head. This disorder, known as benign paroxysmal positional vertigo (BPPV), develops because of free movement of otoconia particles (calcium carbonate crystals normally contained within the utricle and saccule), which act as foreign debris within a semicircular canal. The Dix-Hallpike maneuver, during which the patient’s head is turned 45° to the right or left and lowered below the horizontal plane of an examining table to induce symptoms, can be used to diagnose which side and semicircular canal are dysfunctional. Once the side is determined, repositioning treatments such as the Epley maneuver can remove the otoconia from that semicircular canal and provide lasting remission, although recurrence is not unusual. A fourth clinical pattern for the occurrence of peripheral vestibular dysfunction is a toxic etiology, primarily through the use of aminoglycosides (but also other medications such as chemotherapeutics). Systemic ototoxins typically produce head movement–related oscillopsia and decreased vestibular ocular reflex (VOR) gain bilaterally with little or no nystagmus (ie, vestibular hypofunction without asymmetry).
A very large cerebellopontine angle tumor (eg, vestibular schwannoma or meningioma) may produce Bruns nystagmus, which is a combination of gaze-evoked and peripheral vestibular nystagmus. Initially, as the vestibular nerve is affected, the eyes drift toward the side of the lesion, with a corrective fast phase in the opposite direction. As the lesion enlarges, the ipsilateral brainstem is compressed, causing problems in maintaining ipsilateral eccentric gaze; thus, as the patient looks to the side of the lesion, large-amplitude, lower-frequency gaze-evoked nystagmus is noted, whereas in contralateral gaze, small-amplitude, high-frequency vestibular nystagmus is observed.
Baloh RW. Clinical practice. Vestibular neuritis. N Engl J Med. 2003;348(11):1027–1032.
Fife TD, Tusa RJ, Furman JM, et al. Assessment: vestibular testing techniques in adults and children: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2000;55(10):1431–1441.
Central Forms of Vestibular Nystagmus
Extensive interconnections occur between the central vestibular structures of the brainstem and the phylogenetically older regions of the cerebellum (ie, flocculus, nodulus, and vermis). Therefore, it can be difficult, if not impossible, to determine by clinical examination alone the precise location of some lesions that produce central nystagmus. Although some forms of central vestibular nystagmus do provide good localizing information (Table 9-2), it is often more useful to think of the central vestibular pathways as a single system and to obtain neuroimaging if more specific information about localization is desired. If central vestibular nystagmus is of small amplitude and present only outside primary position, patients may have no visual symptoms.
Table 9-2
Downbeat nystagmus
Downbeat nystagmus is the most common form of central vestibular nystagmus and results from lesions that produce defective vertical gaze holding characterized by an upward drift of the eyes, which is then corrected with a downward saccade. Lesions that cause downbeat nystagmus compromise the vestibulocerebellum (ie, nodulus, uvula, flocculus, and paraflocculus) and diminish the tonic output from the anterior semicircular canals to the ocular motoneurons (meaning that the vertical VOR is asymmetric for up-and-down movements, as distinct from the symmetric horizontal VOR). Downbeat nystagmus may be present in primary position, but in accordance with Alexander’s law, the downbeating movements are usually accentuated in downgaze (especially to either side). Patients usually report oscillopsia, which can be debilitating.
A structural lesion may be associated with downbeat nystagmus, in which case the lesion is often located at the cervical-medullary junction. The most common structural lesion is an Arnold-Chiari type I malformation, a developmental abnormality with posterior fossa crowding and cerebellar tonsillar protrusion into the foramen magnum (Fig 9-2). Lesions at the foramen magnum are best assessed with sagittal magnetic resonance imaging (MRI). In some cases of unexplained downbeat nystagmus, antibodies to glutamic acid decarboxylase have been identified in the blood of affected patients. These antibodies might produce downbeat nystagmus by interfering with the GABAergic neurons of the vestibular complex that normally inhibit the cells of the flocculus.
The differential diagnosis of downbeat nystagmus includes
Arnold-Chiari type I malformation
tumors (eg, meningioma, cerebellar hemangioma) at the foramen magnum demyelination
stroke
cranial trauma
drug toxicity (eg, lithium, anticonvulsants) platybasia
basilar artery impression spinocerebellar degenerations
syrinx of the brainstem or upper cervical spinal cord brainstem encephalitis
paraneoplastic syndrome
impaired nutrition (eg, Wernicke encephalopathy, parenteral feeding, magnesium deficiency) antibodies to glutamic acid decarboxylase
idiopathic
Figure 9-2 Arnold-Chiari type I malformation in a 26-year-old patient who reported a sense of movement of his environment. Downbeat nystagmus was identified as the explanation for his oscillopsia. This sagittal, T1-weighted MRI scan shows herniation of the cerebellar tonsils (arrow) through the foramen magnum. (The level of the foramen magnum is shown by the dotted line.)
Common treatments for downbeat nystagmus used “off label” (ie, for an indication other than those that have received approval from the US Food and Drug Administration) include clonazepam, baclofen, gabapentin, base-out prisms (to induce convergence), memantine, 4-aminopyridine, and 3,4- diaminopyridine—but frequently with little to no success.
Upbeat nystagmus
Upbeat nystagmus is characterized by a downward drifting of the eyes, followed by corrective, upward saccades. Upbeat nystagmus may be caused by lesions in the brainstem (often medulla) or the anterior cerebellar vermis; hence, the lesions may exist at various locations within the posterior fossa. Common causes of upbeat nystagmus include demyelination, stroke, cerebellar degeneration, and tobacco smoking.
Torsional nystagmus
Although peripheral vestibular nystagmus may have a torsional component, purely torsional nystagmus indicates a central lesion. Torsional nystagmus is usually associated with a medullary lesion (eg, syringobulbia, lateral medullary infarction) and may be part of an ocular tilt reaction (see Chapter 8).
Periodic alternating nystagmus
Periodic alternating nystagmus (PAN) is a strictly horizontal nystagmus that oscillates predictably in direction, amplitude, and frequency. For instance, a rightward-beating nystagmus develops progressively larger amplitudes and higher frequencies up to a certain point, then wanes, eventually leading to a short period of downbeat or no nystagmus. Then, the nystagmus reverses direction, with a crescendo–decrescendo pattern that again leads to a short period without nystagmus, to complete the cycle. PAN may be congenital or acquired. The acquired form has a characteristic oscillation cycle of 2–4 minutes. A cursory examination may lead to the erroneous conclusion that the nystagmus is directed to one side only. For this reason, any presentation of nystagmus that is purely horizontal and