Central Forms of Vestibular Nystagmus
Because the central vestibular structures of the brainstem and the cerebellum are extensively interconnected, it can be difficult, if not impossible, to determine the precise location of lesions that produce central nystagmus by clinical examination alone. Although some supranuclear ocular motility disorders provide 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. Central vestibular nystagmus often involves pathways governed by the anterior semicircular canals, posterior semicircular canals, or both. Therefore, isolated vertical or torsional nystagmus is common (in contrast to peripheral vestibular nystagmus, which is characterized by horizontal movements combined with torsional movements). If central vestibular nystagmus is of small amplitude and present only outside primary position, patients may have no visual symptoms.
Table 9-2 Selected Forms of Nystagmus or Oscillatory Movements and Their Most Common Lesion Locations
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, the nodulus, uvula, flocculus, and paraflocculus) and diminish the tonic output from the posterior semicircular canals to the ocular motor neurons. 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 cervicomedullary junction. The most common structural lesion is an Arnold-Chiari type I malformation, a developmental abnormality characterized by posterior fossa crowding and cerebellar tonsillar protrusion into the foramen magnum (Fig 9-3). 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 (GAD) have been identified in the blood of affected patients. These antibodies might produce downbeat nystagmus by interfering with the γ-aminobutyric acid (GABA)-ergic neurons of the vestibular complex that normally inhibit the cells of the flocculus.
The differential diagnosis of downbeat nystagmus includes the following:
Arnold-Chiari type I malformation
syrinx of the brainstem or upper cervical spinal cord
tumors of the foramen magnum (eg, meningioma, cerebellar hemangioma)
basilar artery impression
drug toxicity (eg, lithium, anticonvulsants)
impaired nutrition (ie, Wernicke encephalopathy, parenteral feeding, or magnesium deficiency)
Figure 9-3 An 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 T1-weighted sagittal magnetic resonance imaging (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 off-label treatments (treatments prescribed for an indication other than those that have received approval from the US Food and Drug Administration) for downbeat nystagmus and other central vestibular forms of nystagmus include clonazepam (a GABA receptor agonist), baclofen, gabapentin, memantine, 4-aminopyridine, and 3,4-diaminopyridine (amifampridine). Unfortunately, medical treatment often provides little to no improvement of symptoms. Dalfampridine has been used to treat downbeat nystagmus and may be more efficacious than the similar drug 3,4-diaminopyridine. Baseout prisms (used to induce convergence) can sometimes improve the oscillopsia associated with downbeat 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; thus, the lesions may exist at various locations within the posterior fossa. Common causes of upbeat nystagmus include demyelination, stroke, cerebellar degeneration, and tobacco smoking.
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, completing 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 toward one side only. For this reason, any presentation of nystagmus that is purely horizontal and occurs in primary position should be observed for at least 2 minutes to be certain that the condition is not PAN. A patient with PAN may also demonstrate a periodic alternating head turn (in the direction of the nystagmus) to minimize the nystagmus, in accordance with Alexander’s law.
Acquired PAN is caused by unstable “velocity storage,” typically secondary to vestibulocerebellar disease. As discussed in Chapter 8, the vestibular-ocular system’s response to sustained head rotation attenuates fairly quickly as the cilia on the hair cells resume their normal position. However, a velocity storage mechanism prolongs the vestibular-ocular response for several seconds during sustained head movements. This velocity storage mechanism is generated by interconnections within the vestibular nuclei (the vestibular commissure) and is stabilized by cerebellar GABA-ergic innervation. Cerebellar disease may cause unstable velocity storage that results in a horizontal nystagmus with an oscillating null point, namely PAN. Common causes include Arnold-Chiari type I malformation, cerebellar degeneration, multiple sclerosis (MS), cerebellar tumors, stroke, use of anticonvulsant medication, and bilateral loss of vision. If the bilateral vision loss is reversed (eg, if a vitreous hemorrhage is cleared), PAN may be abolished. Baclofen, a GABA receptor agonist, can abolish the acquired form of PAN.
Excerpted from BCSC 2020-2021 series: Section 5 - Neuro-Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.