Jerk nystagmus

INTRODUCTION — Jerk nystagmus is a rhythmic eye oscillation characterized by a slow drift of the eyes in one direction that is repeatedly corrected by fast movements in the reverse direction. In most cases the slow drift is the problem, of which there are two main causes:

●A tonic imbalance in a "slow eye movement" system, such as the vestibular or pursuit systems. This is most often due to an acute asymmetry in vestibular activity, either peripheral or central. (See "Overview of nystagmus".)

●An inability to hold an eccentric eye position against the normal viscoelastic forces that tend to bring the eye back to midline ("gaze-holding").

In both types, corrective fast eye movements restore the eye to its desired position. These quick or fast phases are likely generated through the same brainstem structures that create saccades.

Jerk nystagmus is subdivided by trajectory and the conditions under which it occurs (table 1). Some forms are always present, even when the eyes are in the primary position. Nystagmus in the primary position is classified according to trajectory: downbeat, upbeat, horizontal, torsional, or mixed. The direction named is the direction of the fast phase. Other forms emerge only under specific conditions such as peripheral gaze (gaze-evoked) and certain head positions (positional). The presence of a subtle primary or position-evoked nystagmus that may be evident only on funduscopy or video-oculography must be interpreted with caution in the asymptomatic subject, as these can be found in a minority of healthy subjects [1].

PRIMARY POSITION JERK NYSTAGMUS — Nystagmus in the primary position is classified according to trajectory: downbeat, upbeat, horizontal, torsional, or mixed.

Downbeat nystagmus

Anatomy — Downbeat nystagmus results from damage to one of two sites:

●Dorsal medulla – This interrupts pathways from both posterior semicircular canals in the floor of the fourth ventricle. The loss of tonic downward vestibular input causes the eyes to drift slowly upward.

●Cerebellar flocculus or its projections – This removes a tonic inhibition of upward vestibular eye movements [2], leading to a similar imbalance of down/up vestibular impulses. This imbalance is thought to reflect a preponderance of downward "on-direction" velocity Purkinje cells in the flocculus [3].

Etiology — Idiopathic downbeat nystagmus occurs in approximately 25 to 40 percent of cases [4-7]. Some of these may be caused by compression of the medulla by dolichoectatic arteries that are now visible with magnetic resonance imaging (MRI) [7,8]. Surgical decompression was successful in one case [8]. In some other idiopathic cases, voxel-based morphometric MRI studies have demonstrated focal atrophy of gray matter in the vermal and lateral cerebellar hemispheres, suggesting a neurodegenerative process [9]. A genome-wide association study of 106 patients found a link between idiopathic downbeat nystagmus and a genetic variation in the fibroblast growth factor 14 (FGF14) gene, which is also implicated in spinocerebellar ataxia type 27 [10].

The four most frequent identifiable causes of downbeat nystagmus are cervicomedullary junction anomalies (Chiari malformation), cerebellar degenerations, multiple sclerosis, and vertebrobasilar infarction (figure 1) [4,5,11]. Medications and alcohol are other relatively common causes.

●The Arnold-Chiari malformation is the most prominent of the developmental anomalies [4,6]. Symptoms begin insidiously during adulthood. Basilar invagination and syringobulbia can also cause a similar picture [7,11,12]. In the symptomatic patient, surgical decompression may improve the nystagmus [12-15]. (See "Chiari malformations".)

●Many hereditary and sporadic cerebellar degenerations can cause downbeat nystagmus [4,5,11,16]. These are predominantly slowly progressive disorders starting in mid-adulthood.

Among the genetically characterized autosomal dominant ataxias, downbeat nystagmus is often found during or between attacks of episodic ataxia type 2 (EA2), which is caused by mutations in a brain-specific P/Q type calcium channel gene on chromosome 19 [17]. EA2 is discussed separately. (See "Overview of the hereditary ataxias", section on 'Episodic ataxia type 2'.)

Downbeat nystagmus has also been reported with spinocerebellar ataxia (SCA) types 6, 17, and 38 [18-20]. SCA6, which is due to excessive triplet repeats in the same calcium channel gene affected in EA2, can have paroxysmal vertigo early in its course, and thus phenotypic overlap with EA2 [21]. (See "Autosomal dominant spinocerebellar ataxias", section on 'SCA6' and "Autosomal dominant spinocerebellar ataxias", section on 'SCA types 9 to 20'.)

Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) has been described in a few case series and may represent a form of spinocerebellar degeneration [22-25]. Downbeat nystagmus is a common feature of this condition, which also includes bilateral vestibular failure, cerebellar ataxia, and a sensory neuronopathy. (See "Overview of cerebellar ataxia in adults", section on 'Autosomal recessive ataxias'.)

●Drugs that cause downbeat nystagmus include lithium, most often as a chronic effect despite normal levels [4,7,26,27], and rarely with acute overdose [27,28]. There may be predisposing conditions such as hypomagnesemia [26], cerebellar degeneration [27], or Chiari malformation [2,29]. Nystagmus can resolve [26,30] or persist [27,31] after stopping lithium.

Anticonvulsants such as phenytoin [5,11,32], carbamazepine [5,11,33,34], lamotrigine [35], and felbamate [36] can cause a subacute downbeat nystagmus; this can occur with serum levels in the therapeutic range [37]. There are usually other cerebellar signs of toxicity, even if serum levels are normal [32]. A decrease in the dose usually leads to resolution.

Alcohol can cause downbeat nystagmus transiently with acute intoxication [38], or chronically from cerebellar degeneration that is often evident on imaging [6,39,40].

●Infarction and demyelination can cause downbeat nystagmus when located in specific areas in the cervicomedullary junction or cerebellum [11,41-43]. (See 'Anatomy' above.)

Other rare causes of downbeat nystagmus include:

●Acquired metabolic/nutritional causes – Wernicke encephalopathy [7,44] and B12 deficiency [45]. Hypomagnesemia can induce a reversible subacute cerebellar syndrome with downbeat nystagmus associated with confusion, seizures, and tachycardia [46]. This should be suspected in the setting of intestinal malabsorption.

●Toxicity from amiodarone [5] or intravenous opioids [47].

●Inherited disorders of metabolism – Cherry-red spot myoclonus, X-linked adrenoleukodystrophy [48].

●Infectious causes – Viral encephalitis [5,49], herpes simplex [50], AIDS [11], tetanus [51].

●Autoimmune conditions – Antiglutamic acid decarboxylase antibodies can be associated with downbeat nystagmus and ataxia, sometimes with stiff-person syndrome as well [52-54].

●Neoplasms – Posterior fossa tumors [5-7,11] and paraneoplastic cerebellar degeneration [4,5,7,55].

●Hydrocephalus – Hydrocephalus can cause a nystagmus that resolves with shunting [56].

●Meniere disease – On very rare occasions, downbeat nystagmus can be present during a vertiginous attack in this condition, violating the rule that downbeat implies central pathology [57].

●Congenital – Congenital downbeat nystagmus is rare and sometimes familial [58,59]. Nystagmus may persist [58] or resolve in early childhood [59]. Walking is delayed but eventually normal.

A fine, downbeat nystagmus has also been described in associated with blue-cone monochromatism, an X-linked recessive condition [60].

●Familial – Familial positional downbeat nystagmus with cerebellar ataxia has been described, with symptoms starting in late adulthood [61]. Another familial condition with episodes of vertical oscillopsia and interictal downbeat nystagmus starting between the ages of 40 and 65 has been described in Taiwan, with linkage to chromosome 13 [62].

Clinical features — Patients with downbeat nystagmus present with blurred vision, oscillopsia (to-and-fro illusion of environmental motion), or gait imbalance [5,6,63]. Other symptoms vary with the etiology. Oscillopsia is usually constant, rarely episodic. A compressive problem such as Chiari malformation [13,64], hydrocephalus [65], or osteophytes [66] should be suspected if oscillopsia is provoked by neck extension or rotation.

On physical examination, downbeat nystagmus occurs in the primary gaze position and increases with down and lateral gaze [2,4]; rarely, it is present only in these eccentric gaze positions [2,67]. Nystagmus may increase when the patient is lying down [4,11,14] or after head-shaking [21].

Other eye movement signs commonly occur with downbeat nystagmus, especially poor downward smooth pursuit [2,4,11,68]. The "floccular syndrome" consists of downbeat nystagmus, gaze-evoked and rebound nystagmus, and abnormal horizontal smooth pursuit [2,11]. Skew deviation (a misalignment of the eyes leading to diplopia) and internuclear ophthalmoplegia are less common [2,6,63,65]. Approximately 85 percent of patients have gait ataxia, but usually there are few other findings on routine examination [4]. However, one case series reported that many individuals with both idiopathic and secondary downbeat nystagmus had comorbid peripheral vestibular deficits and polyneuropathy [5].

Diagnosis — The history in patients with downbeat nystagmus should concentrate upon:

●Medications and alcohol

●Past history of transient neurologic dysfunction suggesting multiple sclerosis

●Family history of gait imbalance and incoordination

The exam should also search for evidence of bilateral vestibular failure, with the head thrust test (figure 2), or showing that visual acuity during head motion is drastically impaired, compared with acuity when the head is still. (See "Evaluation of the patient with vertigo", section on 'Other vestibular signs'.)

Patients should have an MRI scan, with emphasis upon the posterior fossa and sagittal sections through the craniovertebral junction. CT scans of this region are insensitive. If imaging is negative, serum B12, magnesium, and HIV serology should be obtained.

For patients presenting acutely, a trial of intravenous thiamine and glucose should be given and the cerebrospinal fluid (CSF) examined. Testing for herpes simplex virus should be performed on the CSF, and coverage with intravenous acyclovir should be considered until results are known.

Prognosis and treatment — The prognosis depends in large part on the underlying etiology; the cause of nystagmus must be treated if possible. With idiopathic downbeat nystagmus, progression is slow or may not occur at all [6].

For symptomatic therapy, the current preferred treatment is dalfampridine (4-aminopyridine). One randomized controlled study of 17 patients showed benefit with a single dose of dalfampridine [69]. A second randomized trial in 27 patients found that after four days of treatment with dalfampridine, treated patients showed improved visual acuity on some measurements of gait and balance compared with those who received placebo [70]. A number of other reports have reproduced benefit with either dalfampridine or 3,4-diaminopyridine [71-75], although one report noted that three patients did not improve with 4-aminopyridine [76].

Other medications may also be helpful. A pilot study of chlorzoxazone in 10 patients found improved visual acuity and posturography compared with baseline measures [77]. There are also observational reports of benefit with baclofen [78], intravenous anticholinergics [79], clonazepam [16,80], and valproate [30]. These drugs may not improve the gait ataxia and imbalance, however [74].

Prisms can help those whose nystagmus is significantly reduced by divergence, convergence, or upgaze [44].

Upbeat nystagmus — Projections from the anterior semicircular canals, which generate upward vestibular eye movements, travel from the vestibular to ocular motor nuclei via two pathways. One involves the brachium conjunctivum of the cerebellum [81,82]. The second goes through the medial brainstem [16]. Hence, midline lesions of the junction of the pons and medulla or pons and midbrain cause loss of this upward input, with a resulting slow downward drift and upbeat nystagmus [83-85]. In one small study of 15 patients, the most common lesion site was the medulla in eight patients [86]. In the medulla, the nucleus intercalates may be a key site of damage [87,88].

Etiology — The most common causes of upbeat nystagmus are cerebellar degeneration [63,85,89,90] and brainstem/cerebellar stroke (figure 3) [86].

●Cerebellar degeneration can be acquired or hereditary.

●Most strokes are infarctions of the medial medulla [63,91] or paramedian pontine tegmentum [92]. Hemorrhages of the cerebellum [82], pons [93], or medulla [94] also are common.

●Demyelination can cause upbeat nystagmus [83,84,92].

●Brainstem gliomas [85,95,96] or cerebellar tumors, including astrocytoma [85,97], ependymoma [83], medulloblastoma [85], metastases [81], and rarely pinealoma [85], may cause upbeat nystagmus.

Other more unusual causes include the following:

●Infection/inflammation – Viral encephalitis [85,89] and meningitis [98], tuberculoma [83], Behçet syndrome [85], sarcoidosis [83].

●Autoimmune conditions – Upbeat nystagmus, epilepsy, and ataxia have been described with antiglutamic acid decarboxylase antibodies [99]. Upbeat nystagmus was a feature of a paraneoplastic syndrome in a patient with pancreatic cancer without identified paraneoplastic antibodies [100].

●Metabolic – Wernicke encephalopathy [83,101,102], B12 deficiency [103].

●Toxic – Anticonvulsants [85], opiates [104], anticholinesterase insecticides [105].

●Hydrocephalus [86].

●Chiari malformation – While this is a common cause of downbeat nystagmus, it rarely causes upbeat nystagmus. Nevertheless, several reported series of patients with Chiari malformation have noted a patient with upbeat nystagmus among their cohorts [106-108]. (See "Chiari malformations".)

●Congenital [85,89] – Sometimes associated with Leber congenital amaurosis [109]. A transient, sometimes intermittent form more apparent in the supine position and with tonic downgaze deviation occurs in normal infants at approximately six to eight weeks of age and disappears after a few months to one year [110,111].

●Bilateral peripheral vestibular disease – Upbeat nystagmus is rarely seen with this disease [112]. On occasion, a pure upbeat variant of benign paroxysmal positional vertigo can be found with bilateral canalithiasis [113], or bilateral superior canal plugging [114].

Clinical features — Oscillopsia is less frequent with upbeat than with downbeat nystagmus [63]. Patients may complain of blurred vision or can be asymptomatic.

Upbeat nystagmus occurs in the primary position and usually increases with upgaze and decreases with downgaze and sometimes convergence [83,86]. Rarely, it may convert into downbeat nystagmus in upgaze [115] or when the patient is lying down with the neck extended [86]. Impaired upward pursuit is always seen [63]. Other eye movement abnormalities are variable [63], including poor horizontal smooth pursuit [89], gaze-evoked nystagmus in 50 percent [81,89,94,97], and rebound nystagmus [89]. Internuclear ophthalmoplegia [86,92,95], skew deviation, or ocular tilt reaction [86,91,92] are evident in up to half of patients. A video demonstrating upbeat nystagmus following a medial medullary infarction is available at http://www.neuroophthalmology.ca/case-of-the-month/eye-movements/sudden-oscillopsia-bilateral-limb-weakness.

Patients with cerebellar lesions have gait ataxia in 50 percent of cases [89,95], and dysmetria, dysarthria, and truncal ataxia [81,83,89]. In those with medullary lesions, there can be palsies of the pharynx and tongue, tongue fasciculations [94,96,102], palatal myoclonus [93], and pain and temperature loss in the body or face [91].

Diagnosis — The history in patients with upbeat nystagmus should concentrate upon:

●Medications, insecticide exposure, and diet

●Past history of vertigo or transient neurologic dysfunction suggesting multiple sclerosis

●Family history of gait imbalance and incoordination

MRI is the procedure of choice, with emphasis upon the posterior fossa. The CSF should be examined if infection or inflammation is suspected.

Prognosis and treatment — There is no proven treatment for upbeat nystagmus. There are reports of benefit with baclofen [78], alcohol, amytal [116], dalfampridine (4-aminopyridine) [117], memantine, and gabapentin [118]. Prisms might help patients whose nystagmus is minimized by downgaze or convergence. The course is often long-lasting [85].

Horizontal nystagmus — Horizontal nystagmus can occur with acquired peripheral or central vestibular lesions. Congenital nystagmus can also have a horizontal jerk waveform (see "Pendular nystagmus"). A special and unusual central form is periodic alternating nystagmus, which can be congenital or acquired.

Peripheral vestibular lesions — Pure or nearly pure horizontal nystagmus is not uncommon following sudden unilateral loss of labyrinthine inputs from vestibular neuritis or partial neurectomy [119,120]. Neuritis may preferentially affect the inputs of the horizontal semicircular canal, with variable degrees of anterior canal involvement [119]. These two semicircular canals are innervated by the superior division of the vestibular nerve and also have a distinct blood supply, the anterior vestibular artery, which may explain sparing of both posterior semicircular canal function and hearing by a peripheral lesion [121]. A video demonstrating horizontal nystagmus following right vestibular infarction is available at http://www.neuroophthalmology.ca/textbook/e-figures/right-vestibular-hypofunction-from-ischemia-secondary-to-traumatic-vertebral-dissection.

Central vestibular or "pursuit-paretic" horizontal nystagmus — A low-amplitude nystagmus in primary position is sometimes seen in patients with poor pursuit due to large cerebral lesions [122]. The fast phase is towards the side of the lesion. Patients are generally asymptomatic and the small nystagmus is hard to see.

In some cases with unilateral pathology of the vestibular nuclei, horizontal nystagmus beating away from the side of the lesion is combined with abnormal smooth pursuit [123,124]. However, it is not clear that these are related, or whether pursuit merely appears defective because of superimposed nystagmus. These patients usually have vertigo. (See "Evaluation of the patient with vertigo".)

Periodic alternating nystagmus — Patients with periodic alternating nystagmus may complain of regular episodic symptoms of oscillopsia or blurred vision. The horizontal nystagmus beats in one direction for approximately 1 to 2 minutes, stops for 5 to 20 seconds, then beats in the other direction for another 1 to 2 minutes [2,4]. During the oscillation the nystagmus is least when looking in the direction of the slow phase: some patients use this to minimize oscillopsia by alternating their direction of gaze [125]. A video demonstrating congenital periodic alternating nystagmus is available at http://www.neuroophthalmology.ca/case-of-the-month/eye-movements/longstanding-nystagmus.

The cause of periodic alternating nystagmus is thought to be unstable storage of vestibular velocity in the cerebellum, causing hyper-responsive vestibulo-ocular responses [80]. Lesions of the nodulus and uvula in monkeys create a periodic alternating nystagmus in darkness [126].

Periodic alternating nystagmus can be congenital or acquired.

●Congenital forms have similar associations as other types of congenital nystagmus [127-129], including albinism [130] (see "Pendular nystagmus"). It can occur with ataxia-telangiectasia syndrome [131]. An X-linked infantile variant with associated strabismus and refractive errors has been described [132]. A video demonstrating congenital periodic alternating nystagmus is available at http://www.neuroophthalmology.ca/case-of-the-month/eye-movements/longstanding-nystagmus.

●Acquired forms are associated with damage to vestibulocerebellar pathways, particularly Arnold-Chiari malformation [128,129,133] and cerebellar degeneration [128,129,134], including SCA6 [135] (see "Autosomal dominant spinocerebellar ataxias", section on 'SCA6'). Other causes include multiple sclerosis [136]; stroke [137]; tumors; infections such as cryptococcosis, syphilis, and varicella encephalitis [129]; and lithium use [138]. A rare autoimmune case was associated with antibodies against glutamic acid decarboxylase [52], while another was associated with anti-Yo antibodies as part of a paraneoplastic syndrome [139]. Occasional cases are described with visual loss, with nystagmus improving as vision improves [140]. Additional cerebellar signs are common in patients with acquired disease.

Investigation for visual abnormalities is required in patients with the congenital form. With the acquired form, the main investigation is MRI of the brainstem and cerebellum, with consideration of CSF exam if infection is suspected.

The prognosis varies with the underlying condition. In unusual cases, progression of degenerative disease may paradoxically eliminate nystagmus. Baclofen, 10 mg three times daily, is effective treatment for the acquired form [125,141-143]. Baclofen had been thought ineffective for the congenital form [144], but a study of eight patients found some benefit in seven, with three continuing on treatment for several years [145]. In those who do not respond to baclofen, retrobulbar botulinum toxin injections and muscle surgery have been used [146], sometimes with improvement in acuity and oscillopsia [147]. Amantadine 300 mg daily was reported to resolve nystagmus in one patient with acquired periodic alternating nystagmus who did not respond to baclofen [148].

Torsional nystagmus — Torsional nystagmus is a central nystagmus caused by dysfunction of vertical semicircular canal inputs from one side [149] or possibly by otolith dysfunction. Most cases have lesions at the lateral junction of the pons and medulla that involve the vestibular nuclei [149,150]. Vestibular input to ocular motor centers can also be interrupted in the pons [151] or midbrain [152]. Torsional nystagmus can beat either towards or away from the side of the midbrain lesion, depending on which prenuclear ocular motor structure is involved [153].

Etiology — The most common causes of torsional nystagmus are infarction and multiple sclerosis (figure 4) [149,151]. Tumors and venous angiomata in the pons or cerebellum [149,154,155] are next most frequent. Rare causes include encephalitis [149], vascular compression [156], trauma [149,157], syringobulbia [158], and seizures [159,160].

Clinical features — Torsional nystagmus is usually a constant nystagmus with oscillopsia. Episodic torsional nystagmus is rare [156,161].

The torsional movements are the same in both eyes, frequently also with a small vertical movement [150-152,161]. Torsional nystagmus can dampen with convergence [154].

Smooth pursuit is poor [149] and skew deviation is seen in 30 percent of cases [149,152]. Patients with a medullary lesion may have other signs of the lateral medullary syndrome [150]. (See "Posterior circulation cerebrovascular syndromes", section on 'Lateral medullary infarction'.)

Patients with pontine lesions may have internuclear ophthalmoplegia [151,154], and patients with midbrain lesions may have vertical gaze palsies [152].

Diagnosis — MRI of the posterior fossa is required in all patients with torsional nystagmus. CSF examination is not helpful if signs of infection are absent.

Treatment — There is no proven effective treatment. One patient is reported to have improved with alternating trials of memantine and gabapentin [118].

Peripheral nystagmus — Nystagmus due to a peripheral vestibular lesion arises from an acute or intermittent asymmetry in vestibular function, altering the normal "push-pull" balance between antagonistic inputs from the right versus left ear. This usually occurs with unilateral disease. Symmetric, simultaneous bilateral vestibular loss, as with aminoglycoside ototoxicity or bilateral vestibular schwannomas (acoustic neuromas), does not cause vertigo and nystagmus, but rather oscillopsia with head motion [162].

The nystagmus reflects the pattern of semicircular canal dysfunction. (See "Overview of nystagmus".)

●Unilateral vestibular lesions can affect the inputs from all three canals on one side. The resulting nystagmus has a mixed horizontal torsional waveform; either right-beat and clockwise for left-sided disease, or left-beat and counterclockwise for right-sided disease.

●Partial lesions may occur that tend to affect the horizontal and anterior canal together because of the vascular supply and neural divisions in the superior and inferior vestibular nerves. This creates a mixed horizontal, upbeat, and torsional nystagmus, or sometimes a waveform that is almost solely horizontal [119].

Peripheral vestibular nystagmus increases with gaze in the direction of the fast phase, and decreases with gaze in the direction of the slow phase [163]. Some grade nystagmus as first degree (only present on gaze in the direction of the fast phase), second degree (also present in primary position), and third degree (evident even with gaze in the direction of the slow phase). This correlates with severity and duration, to some degree.

Some forms of peripheral nystagmus are due to abnormal excitation of the vestibular system rather than hypofunction [164]. The classic example is benign paroxysmal positional vertigo, which in the majority of cases is due to abnormal excitation of a posterior semicircular canal with certain head positions, leading to a mixed upbeat/torsional nystagmus (see "Benign paroxysmal positional vertigo"). Excitation tends to be restricted to one canal, causing either a mixed vertical/torsional nystagmus if one of the vertical canals is responsible [164,165], or a horizontal nystagmus if the horizontal canal is the site of the lesion [166].

Differentiating central and peripheral nystagmus — Some features can aid in distinguishing peripheral from central vestibular nystagmus (table 2):

●Peripheral nystagmus is often accompanied by severe vertigo and vomiting. The symptoms with central nystagmus range widely from none, to mild oscillopsia, to pronounced vertigo.

●Peripheral nystagmus, even from a permanent lesion, almost always remits within a few days to weeks through central adaptive mechanisms and the development of the ability to suppress nystagmus with visual fixation [167]. Suppression can be demonstrated during funduscopy by covering the remaining viewing eye briefly and seeing if the examined fundus starts to move more. Frenzel lenses that blur vision can be used to show this too. Central nystagmus can be persistent or remitting depending upon the lesion, and is not suppression by fixation.

●The waveform is a valuable clue. Pure downbeat, pure upbeat, or pure torsional nystagmus are almost always central brainstem signs, while pure horizontal or mixed forms of nystagmus typify peripheral disease. However, the presence of pure horizontal or mixed nystagmus cannot exclude central disease since they also occur with lesions of the vestibular nuclei in the lateral medulla. A reversal of nystagmus direction between right and left gaze indicates defective gaze-holding (see 'Gaze-evoked nystagmus' below) and points to a central cause [168].

●Accompanying hearing loss is common with peripheral nystagmus but rare with central lesions. Conversely, cerebellar and brainstem signs indicate a central lesion. However, a lack of these features cannot be used to exclude locations.

GAZE-EVOKED NYSTAGMUS — Gaze-evoked nystagmus is probably the most commonly encountered type of nystagmus. To maintain an eccentric eye position, increased tonic contraction of the agonist muscles is needed to oppose the elastic forces that bring the eye back to center. This "step" increase in neuronal firing and muscle contraction normally correlates well with the large "pulse" of force that shifted the eye to that position. An inadequate step after a pulse will cause the eyes to drift back to center.

The structures involved in gaze-holding are the cerebellar flocculus, along with regions in the lateral medulla for horizontal gaze and the midbrain for vertical gaze. Rebound nystagmus (see 'Clinical features' above) may represent a short-term adaptation by intact vestibulo-ocular pathways to counteract gaze-evoked nystagmus [169].

Etiology — Causes of gaze-evoked nystagmus include the following:

●Gaze-evoked nystagmus is part of the "floccular syndrome." (See 'Downbeat nystagmus' above.)

●Toxic/metabolic causes, the most common, include anticonvulsants such as phenytoin, as well as lithium, and sedatives.

●Structural causes include spinocerebellar degeneration, multiple sclerosis, cerebellar or brainstem ischemia, and posterior fossa tumors [168,170].

●Autoimmune cerebellar syndromes such as gluten sensitivity with antigliadin antibodies [171].

●Autosomal dominant spinocerebellar ataxias (SCAs), including SCA6, SCA15, and SCA28, among others [172-174], as well as episodic ataxia type 2 (EA2) [175]. Gaze-evoked nystagmus is occasionally seen in muscle and nerve disorders such as myasthenia gravis [176] and the Miller-Fisher syndrome.

Clinical features — Only a minority of subjects with severe gaze-evoked nystagmus complain of gaze-evoked oscillopsia. Most are asymptomatic or have other complaints, such as poor balance from gait ataxia.

Physical examination may reveal the following:

●Relatively large-amplitude (greater than four degrees) nystagmus beating in the direction of gaze [170]. This must be contrasted with normal endpoint nystagmus, in which a small degree of nystagmus in extreme gaze is seen in 50 percent of normal subjects [177], particularly in darkness. Physiologic endpoint nystagmus also tends to fatigue with prolonged end-gaze.

●Rebound nystagmus – Lateral gaze for approximately a minute leads to a decrease of nystagmus in some patients, and when the eyes return to center there is a transient nystagmus in the opposite direction, fading over several seconds. This almost always indicates a vestibulocerebellar lesion [169,178-181].

A video demonstrating gaze-evoked and rebound nystagmus in a patient with EA2 is available at http://www.neuroophthalmology.ca/case-of-the-month/eye-movements/intermittent-imbalance-and-a-mother-with-cerebellar-degeneration.

●Associated signs – Impairment of horizontal pursuit is common [168], sometimes with other elements of the floccular syndrome (eg, downbeat nystagmus). Other cerebellar dysfunction such as gait ataxia may be present.

Diagnosis — Medications must be reviewed first in patients with gaze-evoked nystagmus. Magnetic resonance imaging (MRI) with focus on the posterior fossa and consideration of demyelination is recommended next.

Differential diagnosis — First-degree vestibular nystagmus is only seen when the eyes are looking to the side opposite the vestibular lesion. In contrast with the nystagmus from impaired gaze-holding, there is no nystagmus in the opposite direction; thus, gaze-evoked nystagmus in both directions implies a central lesion.

Dissociated gaze-evoked nystagmus is a manifestation in the normal eye of central adaptation to ocular motor weakness in the other eye. This is most commonly seen in internuclear ophthalmoplegia and occasionally with VI and III nerve palsies. In internuclear ophthalmoplegia, there is a failure of adduction in one eye coupled with an abducting nystagmus in the fellow eye.

Prognosis and treatment — Gaze-evoked nystagmus often resolves when the offending drug is stopped. Treatment is not usually needed. Associated balance problems may require physical therapy.

Bruns (bidirectional horizontal) nystagmus — Bruns nystagmus is a combination of mild horizontal vestibular nystagmus (usually contralateral to the lesion) in one direction of gaze, and a coarser impaired gaze-holding nystagmus in the other direction [14]. It is often accompanied by other central eye movement abnormalities, including impaired pursuit and optokinetic responses, hypermetria of saccades, and gaze-evoked nystagmus in upgaze [182]. A video demonstrating Bruns nystagmus is available at http://www.neuroophthalmology.ca/case-of-the-month/eye-movements/diplopia-and-an-unusual-nystagmus.

Bruns nystagmus indicates a lesion at the cerebellopontine angle, which can impair both the gaze-holding network and the vestibular input from one side. It is usually caused by tumors compressing the brainstem [182] and is seen in 15 percent of patients with cerebellopontine angle tumors, which are often vestibular schwannomas (acoustic neuromas), but also meningiomas [183], astrocytomas [184], epidermoid tumors, arachnoid cysts, and vertebral aneurysms [185]. It also occurs rarely with disease in the brainstem, such as multiple sclerosis [186] or lateral medullary infarcts [187,188].

MRI of the posterior fossa is indicated in patients with Bruns nystagmus. The tumors that cause this disorder are always large (diameter greater than 3 cm) since brainstem compression is required [183]. Two-thirds of patients also have abnormal brainstem auditory evoked responses [183].

Neurosurgical treatment is required in most patients. The prognosis varies with the etiology.

LATENT NYSTAGMUS — Congenital nystagmus can have both pendular and jerk characteristics, even within the same patient. Nystagmus also can change with the direction of gaze.

Latent nystagmus is a particular type of congenital nystagmus that is a horizontal jerk nystagmus. Latent nystagmus is found in patients with childhood strabismus. It is a nystagmus that changes or appears only with monocular viewing.

Neonates viewing with one eye only have an asymmetry in the optokinetic eye movements to nasally versus temporally moving stimuli. Latent nystagmus may reflect persistence of this asymmetry in patients who fail to develop binocular vision because of strabismus [189]. Monkeys raised without binocular vision develop latent nystagmus; some suggest that this is due to the failure to develop binocular innervation of midbrain regions that generate optokinetic responses [190,191]. Others suggest that the key problem is loss of binocular connections to striate cortex in the first months of life, and that the nystagmus results from an imbalance in binocular activity in cortical regions such as the medial superior temporal area [192].

There is evidence that manifest latent nystagmus emerges only in the absence of binocular vision since it often resolves when binocular vision is established [193].

Clinical features — Latent nystagmus is asymptomatic. When one eye is covered, a conjugate jerk nystagmus appears, beating in the direction of the viewing eye (eg, left beating with left eye viewing alone). When the other eye is covered, the nystagmus reverses direction. With both eyes open there may be no nystagmus (true latent nystagmus) or, particularly in patients with amblyopia, there may be a smaller nystagmus beating towards the preferentially viewing eye (manifest latent nystagmus). A video demonstrating latent nystagmus is available at http://www.neuroophthalmology.ca/case-of-the-month/eye-movements/longstanding-nystagmus-2.

Eye movement recordings show that all latent nystagmus has a small manifest component [194,195]. Nystagmus often begins as manifest in infants, gradually converting to a more latent form [196].

In addition to nystagmus, there are a number of associated signs in patients with latent nystagmus:

●Strabismus is common, mostly esotropia, sometimes exotropia, and rarely only phoria [195].

●Many patients have "dissociated vertical deviation," meaning that each eye when covered deviates upward.

●Horizontal pursuit and optokinetic responses are variably affected. With monocular viewing, the response to stimuli moving temporally (from nose to temple) may be decreased; whether this causes or is caused by the nystagmus is debated [197].

Evaluation and diagnosis — The pattern of nystagmus is pathognomonic. No diagnostic testing is required.

Manifest latent nystagmus can be confused with other horizontal jerk nystagmus until it is appreciated that the nystagmus reverses direction when the preferred eye is covered.

Prognosis and treatment — Latent nystagmus persists throughout life. In a few patients it is worsened nonspecifically by unrelated diseases or minor head injury [195], causing confusion until the characteristic effect of monocular viewing is discovered.

Manifest latent nystagmus can be converted to latent nystagmus in patients with a good result from strabismus surgery or correction of refractive error, leading to better binocular visual acuity [193].

Latent nystagmus is not necessarily a contraindication to patch therapy in children with strabismus [198]. Patching over a few days can actually decrease oscillopsia and nystagmus in the viewing eye [199].

SUMMARY

●Definition and clinical features – Jerk nystagmus is a rhythmic eye oscillation characterized by a slow drift of the eyes in one direction, repeatedly corrected by fast movements in the reverse direction. In most cases the slow drift represents the problem, of which there are two main causes:

•A tonic imbalance in a "slow eye movement" system, such as the vestibular or pursuit systems. This is most often due to an acute asymmetry in vestibular activity, either peripheral or central.

•An inability to hold an eccentric eye position against the normal viscoelastic forces that tend to bring the eye back to midline ("gaze-holding").

●Classification – Jerk nystagmus is subdivided by trajectory and the conditions under which it occurs (table 1).

•Primary position nystagmus – Nystagmus in the primary position is classified according to trajectory: downbeat, upbeat, horizontal, torsional, or mixed. (See 'Primary position jerk nystagmus' above.)

The anatomic location and likely underlying etiology vary according to these classifications. Intoxications, structural lesions (infarction, demyelination, tumor) in the brainstem, and degenerative disease are usually in the differential diagnosis. Magnetic resonance imaging (MRI) is usually helpful.

Treatment depends on the underlying cause as well as the classification.

•Gaze-evoked nystagmus – This can occur as a result of toxins, structural pathology in the cerebellum or brainstem, as well as with some muscle and nerve disorders. Most patients are asymptomatic or have mild ataxia. The treatment is that of the underlying disorder or removal of the offending medication. (See 'Gaze-evoked nystagmus' above.)

•Latent nystagmus – Patients with childhood strabismus may be observed to have a latent nystagmus, brought out on monocular examination; with both eyes open there may be no nystagmus. In addition to strabismus, many patients have dissociated vertical deviation and/or abnormal horizontal pursuit or optokinetic responses. (See 'Latent nystagmus' above.)