Acquired

BASICS


DESCRIPTION


• Acquired nystagmus is a repetitive, rhythmic, involuntary oscillation of the eyes, and can be constant, cyclical, or intermittent.


• All nystagmus occurs of a result of the eyes drifting from the desired position of gaze.


• It can be monocular, binocular, or asymmetric (dissociated).


• Nystagmus can be directionally symmetrical with a sinusoidal (pendular) waveform, or it can have a slow drift and a rapid corrective “jerk” component.


• The slow drift can have a linear, exponentially increasing, or exponentially decreasing (decaying) waveform.


EPIDEMIOLOGY


Prevalence


• The prevalence of nystagmus is estimated at 240/100,000 based on a community survey in Leicestershire, UK.


RISK FACTORS


• As acquired nystagmus can occur as a result of a variety of conditions, no specific risk factors can be cited.


Genetics


• A variety of inherited conditions can have nystagmus as part of the spectrum of central nervous system manifestations.


GENERAL PREVENTION


• Prevention measures for acquired nystagmus depend on the specific etiology of the nystagmus.


PATHOPHYSIOLOGY


• Optimal visual acuity requires image motion on retina to be <5 degrees/second. Three main mechanisms hold gaze steady:


– Vestibulo-ocular reflex


– Visual fixation


– Eccentric gaze-holding mechanisms, so-called “Neural integrator.”


• Visual fixation has 2 components:


– Corrective eye movements in response to retinal image drift, and


– Suppression of unwanted movements that move eyes away from target


• Eccentric gaze-holding mechanisms: The neural integrator is a diffuse system comprising the vestibulocerebellum and cell groups in paramedian tracts, including the medial vestibular nucleus (MVN) and the adjacent nucleus prepositus hypoglossi (NPH) in the medulla for horizontal gaze, and the interstitial nucleus of Cajal (INC) in the midbrain for vertical gaze.


• A pulse of innervation to the extraocular muscles (EOMs) is needed to overcome viscous drag (mediated by burst neurons); a step of innervation to EOMs is needed to overcome elastic restoring forces (mediated by tonic neurons) and keep the eyes from slipping back.


• The saccadic pulse generator for horizontal gaze is located in the ipsilateral paramedian pontine reticular formation (PPRF) in close proximity to the abducens nucleus.


• Ocular motor neurons receive input from both burst and tonic cells in the PPRF neural integrator to achieve correct burst-tonic firing pattern.


• The most common type of pulse-step disorders include mismatch (glissade), where the step is smaller than the pulse, and gaze-evoked nystagmus (due to a variety of toxins, most commonly ethanol), where the step is poorly sustained. Both these conditions lead to nystagmus in eccentric gaze, with slow phases directed toward the primary position.


ETIOLOGY


• Nystagmus can be classified according to the following scheme:


Peripheral vestibular nystagmus: Benign paroxysmal positional vertigo (BPPV)


Central vestibular nystagmus: Downbeat, upbeat, and torsional


Nystagmus due to vestibular instability: Periodic alternating nystagmus (PAN)


Nystagmus caused by disorders of visual fixation: See-saw nystagmus. Disorders of the anterior visual pathways often cause nystagmus due to both loss of visual motion information that can be used to compensate for drifts of eyes off target, and loss of visual input essential to “calibrate” normal eye movements.


Nystagmus caused by disorders of gaze holding: Acquired pendular nystagmus, gaze-evoked nystagmus, oculopalatal tremor or “myoclonus.”


COMMONLY ASSOCIATED CONDITIONS


• Nystagmus is often accompanied with other neurological findings such as vertigo and ataxia.


DIAGNOSIS


HISTORY


• Acquired nystagmus is accompanied with oscillopsia, or apparent movement of stationary objects. This can become severe enough to degrade visual acuity.


PHYSICAL EXAM


Benign paroxysmal positional vertigo (BPPV):


– Most commonly due to posterior canal disease


– Mixed horizontal and torsional nystagmus


– Waveforms have linear slow phases.


– Unidirectional, obeys Alexander’s law (amplitude greater when eyes turn toward direction of jerk component)


– Suppressed with fixation, worse under Frenzel glasses


– Fatigues easily, resolves in days to weeks


Downbeat nystagmus: The vestibulocerebellum inhibits central connections from the anterior canals (which are activated by neck flexion and move eyes up), but not from the posterior canals (which are activated by neck extension and move eyes down).


– Lesions of the vestibulocerebellum (such as Arnold-Chiari malformation) cause disinhibition of the anterior canal projections, causing eyes to drift upward, and compensatory downward nystagmus to occur.


– Other etiologies include M.S., medication toxicity (lithium, antiepileptic meds, opioids, amiodarone), deficiency states (B12, thiamine, magnesium), toluene abuse, craniocervical junction pathology (stroke, trauma, or bleed), hydrocephalus, paraneoplastic cerebellar degeneration due to anti-Ta antibody, stiff person syndrome.


– Cortical projections to vestibulocerebellum are GABAergic, so benzodiazepines can be used (e.g. Clonazepam), as well as baclofen, a GABA-β agonist.


– 3,4-diaminopyridine (3,4-DAP; amifampridine), a potassium channel blocker, has been shown to suppress downbeat nystagmus. This agent is currently only available in Europe. A related agent, 4-aminopyridine (fampridine, dalfampridine, Ampyra) is now commercially available in the US.


– Downbeat nystagmus due to Episodic Ataxia type 2, due to a P/Q type calcium channel (CACNL1A4) mutation, responds to acetazolamide.


Upbeat nystagmus: Pathology usually lies in medial medullary tegmentum (nucleus intercalatus).


– It is caused by M.S., brainstem strokes, cerebellar degenerations, Wernicke’s, Behcet’s, paraneoplastic, Leber’s congenital amaurosis, toxins (organophosphates, anticonvulsants, cyclosporine A), smoking (in the dark only).


Torsional nystagmus: Associated with the ocular tilt reaction and skew deviation. This is a rare condition, and no data on treatment exists.


PAN (Periodic alternating nystagmus):


– Shifts direction every 80–120 seconds


– Etiology is similar to that of downbeat nystagmus.


– Relieved by baclofen, a GABA-β agonist. This has been thought to be due to baclofen’s ability to compensate for loss of cerebellar inhibition, but an NMDA effect may also be involved.


Disorders of the anterior visual pathways often cause nystagmus (e.g., see-saw). This is thought to be due to both loss of visual motion information that can be used to compensate for drifts of eyes off target, and loss of visual input essential to “calibrate” normal eye movements.


See-saw Nystagmus: Dysconjugate vertical movements; upward moving eye intorts, downward eye extorts


– Usually due to parasellar lesions, possibly due to midbrain compression; also, occasionally with congenital chiasm abnormalities.


Acquired pendular nystagmus: Hallmark of M.S. Other etiologies include stroke, bleed, tumor, Pelizaeus Merzbacher disease, mitochondrial disorders, Cockayne syndrome, toluene abuse, adrenoleukodystrophy.


– May be diagonal, circular, or elliptical.


– Initially thought to be due to visual deprivation, it is now thought to be due to gaze-holding deficits.


– GABA and glutamate receptors are thought to be involved.


Gaze-evoked nystagmus: Present in extremes of gaze (except downgaze). It is due to cerebellar dysfunction (in the flocculus and its connections)


– Most commonly due to sedative–hypnotic drugs.


– It exhibits decelerating slow phases.


Oculopalatal tremor or “myoclonus”: This is another type of acquired pendular nystagmus, vertical-torsional (with unilateral lesions), or vertical (with bilateral lesions).


– Associated with lesions of the Central Tegmental Tract, which runs from the dentate nucleus to the contralateral red nucleus to the contralateral inferior olivary nucleus (“Mollaret’s triangle”); the latter nucleus appears hypertrophic on imaging.


– Frequency is 1–3 Hz.


– Often accompanied by tremor of palate of other branchial muscles.


DIAGNOSTIC TESTS & INTERPRETATION


Lab


Initial lab tests

• Routine lab testing is not useful in acquired nystagmus, as history of toxic exposure, physical examination, and imaging are usually sufficient. Urine drug screening and ethanol level are useful in diagnosing intoxications.


Imaging


Initial approach

• Magnetic resonance imaging of the posterior fossa is usually diagnostic. Diffusion-weighted imaging, FLAIR, and post-contrast T1 imaging are most helpful.


DIFFERENTIAL DIAGNOSIS


Saccadic intrusions: These are arrhythmic, chaotic movements made up of saccadic movements only, with and without intervening periods of ocular rest.


– Saccadic intrusions include square-wave jerks, macrosaccadic oscillations, opsoclonus, and ocular flutter.


Superior oblique myokymia: Intermittent, brief monocular oscillopsia due to small amplitude contraction of the superior oblique.


– Idiopathic, related to microvascular compression of the trochlear nerve


Ocular neuromyotonia: Episodic monocular deviation caused by overaction of a muscle innervated by the oculomotor nerve, usually adduction, brought on by eccentric gaze.


– Patients usually have received radiation therapy to the parasellar region.


TREATMENT


MEDICATION


First Line


Vestibular nystagmus: Current practice guidelines discourage routine medical therapy, especially with benzodiazepines and antihistamines


Downbeat nystagmus: Clonazepam 0.5–1 mg t.i.d, baclofen 5–10 mg t.i.d, trihexyphenidyl 20–40 mg/d


Downbeat nystagmus with episodic ataxia: Acetazolamide 500–1000 mg/d, dosed b.i.d or t.i.d.


Upbeat nystagmus: Baclofen 5–10 mg t.i.d.


Periodic alternating nystagmus: Baclofen 5–10 mg t.i.d.


See-saw nystagmus: Baclofen 5–10 mg t.i.d, clonazepam 0.5–1 mg t.i.d, gabapentin 1200–2400 mg/d dosed t.i.d or q.i.d.


Acquired pendular nystagmus: Gabapentin 1200–2400 mg/d dosed t.i.d or q.i.d, memantine 20–40 mg/d dosed b.i.d or t.i.d, clonazepam 0.5–1 mg t.i.d, trihexyphenidyl 20–40 mg/d, scopolamine (Transderm Scop) 1.5 mg 3-day patch.


Oculopalatal tremor: Gabapentin 1200–2400 mg/d dosed t.i.d or q.i.d, valproate 10–60 mg/kg daily, and trihexiphenidyl 20–40 mg/d.


Second Line


Vestibular nystagmus: Medications used to treat severe vertigo and nausea due to BPPV include antihistamines, anticholinergics, phenothiazines (promethazine, prochlorperazine), benzodiazepines, and ondansetron. They should not be used for more than 48 hours to prevent delay in healing due to CNS compensation.


Downbeat or upbeat nystagmus: Dalfampridine (Ampyra) 20–30 mg/d dosed b.i.d or t.i.d; amifampridine (Zenas, Firdapse) 40–80 mg/d.


See-saw nystagmus: Ethanol 1.2 mg/kg.


Acquired pendular nystagmus: Cannabis, ethanol 1.2 mg/kg.


ADDITIONAL TREATMENT


General Measures


• Peripheral nystagmus and vertigo due to semicircular canal involvement is usually self-limited. It can be improved by various canal repositioning maneuvers (e.g., Epley and Semont maneuvers).


Additional Therapies


• Base-down prisms can be used for downbeat nystagmus, as it damps with upgaze.


• Retinal image stabilization, which consists of high-negative contact lenses coupled with high-positive spectacle lenses, optically reduces acquired pendular nystagmus amplitude.


• Botulinum A toxin injections in extraocular muscles have been reported to be successful in small case studies, but the potential for side effects (ptosis, vertical deviations, worsening of nystagmus in noninjected eye) have prevented the widespread acceptance of this technique.


COMPLEMENTARY & ALTERNATIVE THERAPIES


• None are effective


SURGERY/OTHER PROCEDURES


• Kestenbaum procedures to move eyes into a position that minimizes the nystagmus can be useful, for example, move eyes up for downbeat nystagmus


ONGOING CARE


PROGNOSIS


• Established nystagmus generally persists, except for BPPV, which is a self-limited condition


ADDITIONAL READING


• Baugh RE, Orvidas L, et al. Clinical practice guideline: benign paroxysmal positional vertigo. Otolaryngol Head Neck Surg 2008;139(5 Suppl 4): S47–S81.


• Brandt T, Dieterich M. Vestibular syndromes in the roll plane: topographic diagnosis from brainstem to cortex. Ann Neurol 1994;36(3):337–347.


• Hertle RW. Nystagmus in infancy and childhood. Semin Ophthalmol 2008;23:307–317.


• Lee AGT, Brazil PW. Localizing forms of nystagmus. Symptoms, diagnosis and treatment. Curr Neurol Neurosci Rep 2006;6:414–420.


• Leigh RJ, Tomsak RL. Drug treatments for eye movement disorders. J Neurol Neurosurg Psychiatry 2003;74:1–4.


• Leigh RJ, Zee DS. The Neurology of Eye Movements, Fourth Edition; New York: Oxford University Press, 2006:475–558.


• McLean RJ, Gottlob I. The pharmacological treatment of nystagmus: A review. Expert Opin Pharmacother 2009;10(11):1805–1816.


• Rucker JC. An update on acquired nystagmus. Semin Ophthalmol 2008;23;91–97.


• Rucker JC. Pearls: Nystagmus. Semin Neurol 2010;30:51–53.


• Sarvananthan N, Surendran M, Roberts EO, et al. The prevalence of nystagmus: The Leicestershire nystagmus survey. Invest Ophthalmol Vis Sci 2009;50:5201–5206.


• Straube A, Leigh RJ, Bronstein A, et al. EFNS task force – therapy of nystagmus and oscillopsia. Eur J Neurol 2004;11:83–89.


CODES


ICD9


379.50 Nystagmus, unspecified


CLINICAL PEARLS


• Jerk nystagmus can be physiologic, occurs in extreme lateral eye positions, is of low amplitude and high frequency, and resolves when eyes are removed from extreme lateral gaze.


• Acute onset of gaze-evoked or upbeat nystagmus with confusion and ataxia suggests Wernicke’s encephalopathy.


• Both peripheral and central vestibular nystagmus worsen when the patient looks in the direction of the fast phase (Alexander’s Law).


• Visual fixation suppresses vestibular nystagmus, but worsens infantile nystagmus.


• Jerk nystagmus can be seen with retinal disorders, whereas pendular nystagmus usually is seen with optic nerve disorders.


• Nystagmus associated with visual loss is usually more severe in the eye with worse vision.


• Ophthalmologic examination may reveal a very low amplitude nystagmus, and prolonged observation reveals direction reversal in PAN.


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Nov 9, 2016 | Posted by in OPHTHALMOLOGY | Comments Off on Acquired

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