9 - Nystagmus and Eye Movement Disorders

Question 1

Nystagmus and Abnormal Eye Movements - Introduction

Answer 1

1. Variety of diseases, drugs may disrupt ocular stability
2. Abnormal eye movements may occur due to inability to maintain fixation, loss of normal inhibitory influences on eye movement or control, loss of normally symmetric input from vestibular pathways to ocular motor nuclei
3. Patients with acquired nystagmus may report oscillopsia → sensation of environment moving
4. Children with early-onset nystagmus have no oscillopsia
5. Nystagmus in primary position may degrade visual acuity
6. Should ask patients with nystagmus for associated neurological symptoms → weakness, numbness, vertigo, ataxia, family history of strabismus or abnormal eye movements
7. Examination of abnormal eye movements → primary gaze and cardinal positions
   
   1. Monocular or Binocular
   2. Conjugate (equal in both eyes)
   3. Horizontal, Vertical, Torsional, Mixed
   4. Continuous or induced by particular eye position
   5. Slow phase only, fast and slow phase, fast phase only
   6. Reduced at null point (field of gaze where nystagmus minimal)
8. Dissociated OR Disconjugate nystagmus → when amplitude of oscillations differs in each eye
9. Disjunctive nystagmus → when direction of oscillations differs between 2 eyes

Question 2

Nystagmus

Answer 2

1. Nystagmus → Rhythmic, to-and-from (horizontal, vertical, torsional, mixed) eye movements that incorporate a slow phase
2. Jerk Nystagmus → Slow phase drift from fixation followed by corrective saccade back to target quickly. Named for fast-phase but slow phase component indicates pathology
3. Pendular Nystagmus → Back-and-forth slow phase movements that occur with no fast phase

• Few beats of nystagmus normally present at extremes of horizontal gaze especially in older adults → not pathological unless persistent, asymmetric or accompanied by other features
• Assessment for subtle nystagmus → Frenzel goggles, 20D lens, SLE, direct ophthalmoscope can block patient’s fixation and magnify abnormal eye movements, ocular motor reading

Question 3

Saccadic Movements

Answer 3

1. No slow phase!
2. Square Wave Jerks
   
   1. Most common in older people
   2. Small, intrusive saccades away from and back to target with normal intersaccadic interval
   3. <2 degrees
   4. Typically 4-6 per minute
   5. Pathological → > 15 per minute
3. Macrosquare Wave Jerks
   
   1. Always pathological
   2. Less common
   3. 5-15 degrees
   4. Larger amplitude and higher frequency than square wave jerks with normal intersaccadic interval
   5. Cerebellar disease or MS
4. Macrosaccadic Oscillation
   
   1. Large saccades that straddle and overshoot fixation without foveation of target with normal intersaccadic interval
   2. Cerebellar disease → tumor, stroke, MS, paraneoplastic syndromes
5. Ocular Flutter
   
   1. Lack intersaccadic interval (break time)
   2. Bursts of involuntary, small amplitude, high frequency (10-15Hz) horizontal eye movements
6. Opsoclonus aka saccadomania
   
   1. Lack intersaccadic interval
   2. Involuntary, multidirectional movements with high freauency but larger amplitude
7. Patient may have opsoclonus and ocular flutter during course of disease
   
   1. Both can occur with myoclonus and ataxia
   2. Opsoclonus may be transient and resolves by 6 months of age
   3. Can be diagnosed definitively with eye movement recordings
   4. Related to cerebellar/brainstem dysfunction that inhibits pause cells located in Pons (pause cells), and activates burst neurins resulting in uncontrolled involuntary, horizontal and vertical saccades. Cerebellum (connections to Pons) also damaged.
   5. Etiology → paraneoplastic syndromes, encephalitis, drug toxicity, MS, hyperosmolar coma, idiopathic
   6. Should look for tumor or paraneoplastic processes
      
      1. Neuroblastoma in children
      2. Small-cell carcinoma in adults
      3. Physical exam and MRI or CTH, chest, abdomen, whole-body PET scan, LP, urine catecholamines
      4. Abnormal paraneoplastic Ab may be found ⇒ anti-neuronal nuclear ab type 2 ANNA-2 or anti-Ri, ANNA-1 or anti-Hu (children with neuroblastoma)
   7. Tx → immunomodulatory drugs may reduce saccadic oscillations
      
      1. Medications including propranolol, verapamil, gabapentin, thiamine

Question 4

Infantile Nystagmus AKA Congenital Nystagmus

Answer 4

1. Often recognized in first few months of life but may not become evident until several years
2. May be family history
3. Almost always conjugate (equal in both eyes) and horizontal even in upgaze or downgaze
4. Nystagmus → continuous OR intermittent, jerk OR pendular in different gaze positions
5. Movements usually with brief periods where eyes are still and aimed at target → foveation periods
6. Frequently a null point → field of gaze where nystagmus minimal and vision during foveation period maximized. If null point not in primary position then patient adopts head turn or posture that places eye in null position to improve vision. (Gaze opposite to direction of fast phase & head tilt towards same side direction of fast phase)
7. Visual attention and fixation usually amplify infantile nystagmus while convergence on near target dampens amplitude of nystagmus
8. INS gone during sleep!
9. 2 characteristic signs
   
   1. Reversal of normal nystagmus on OKN testing → slow-phase movements in opposite direction of rotating OKN drum
   2. Slow-phase velocity increases exponentially with distance from fixation
10. No oscillopsia since in children
11. Visual Acuity determined by length of foveation period + accompanying afferent pathway disease if present. VA often reduced though some have normal VA. Strabismus may occur in 30% of patients

Question 5

Infantile Nystagmus

Answer 5

1. Associated with condition that cause BILATERAL pre-LGN vision loss prior to 2 years of age
2. Work-up for early-onset nystagmus should search for pre-LGN causes
3. Sometimes causes obvious → bilateral cataracts
4. If no obvious structural abnormality then evaluation for other conditions necessary:
   
   1. Optic neuropathy → bilateral optic neuropathy prior to 2 years of age most commonly optic nerve hypoplasia, consider neuroimaging to detect hydrocephalus or compressive lesion. If optic nerve hypoplasia detected then endocrinology evaluation for associated hypopituitarism warranted
   2. Foveal hypoplasia → Patients with albinisma or aniridia. Assess for albinism sequelae including TID, hypopigmentation of RPE/choroid/skin/hair
   3. Retinal dystrophy → INS may occur with early-onset retinal dystrophies such as achromatopsia and Leber congenital amaurosis. Should assess for photophobia, eye pressing, paradoxical pupils, high refractive error. May see ON pallor, vessel atenuation or normal DFE. Ask about family history. Ultimately, ERG required for diagnosis.Children with regression of developmental milestones require further workup for neurometabolic disease
5. 40% of children will have no detectable afferent pathway abnormality despite extensive workup
6. Memantine or Gabapentin may reduce severity of nystagmus and improve visual function in some patients though may have adverse side effects. Base out prisms may be used to induce convergence and may help patients whose nystagmus dampens with convergence. CL may help vision.
7. Anderson-Kestenbaum procedure → LR-MR recession-resection + LR-MR resection-recession on other sidd in order to mechanically shift null point closer to primary position
8. Patients with vertical null point may try surgery though may develp diplopia postoperatively because of limited vertical fusional amplitudes

Question 6

Latent Nystagmus AKA Fusional Maldevelopment Nystagmus

Answer 6

1. Early-onset, conjugate, horizontal jerk nystagmus
2. Accentuated by monocular fixation and stable during fusion of both eyes
3. When 1 eye occluded and eliminating fusion → fixating eye slowly drifts towards occluded eye with corrective abducting saccade. Occluded eye moves in same direction and amplitude (conjugate). Fast phase of both eyes → towards fixating eye. Fast phase reverses when occlusion alternates.
4. When occluder used to check VA, acuity degraded by induced nystagmus → need to partially blur 1 eye with high plus lens which may not induce latent nystagmus and permit better VA measurement
5. Latent nystagmus may occur when both eyes open and 1 eye is suppressed → termed manifest latent nystagmus. Thus clinician may not need to occlude an eye to induce nystagmus
6. Occurs with any condition that disrupts binocular development in first 6 months of life MOST COMMONLY infantile esotropia
   
   1. Severe anisometropia, infantile exotropia, monocular cataract, corneal opacities, unilateral microphthalmos
7. If 1 eye with severe structural damage with poor vision then other eye will be fixating eye and fast phase toward good eye.
8. Patients may maintain a head turn toward fixating eye → head posture places fixating eye in adduction and thus dampens nystagmus in order to improve vision
9. May see associated signs of abnormal binocular involvement → dissociated vertical deviation, oblique overaction, smooth pursuit asymmetry (fixating eye able to pursue target moving toward nose but difficulty [ursuing target away from nose)
10. Latent nystagmus has constant-velocity or decelerating slow phase Vs. increasing exponential waveform of infantile nystagmus.
11. Latent nystagmus and Infantile nystagmus may co-exist

Question 7

Heimann-Bielschowsky Phenomenon

Answer 7

1. Monocular nystagmus in long-standing poor vision
2. May not remit even if visual problem (dense cataract) corrected
3. Nystagmus → intermitent, monocular, vertical, slow, pendular with low frequency and variable amplitude
4. Etiology obvious → no additional testing required
5. Monocular vertical nystagmus in infant with APD and optic nerve atrophy → suggests optic nerve or chiasmal tumor (glioma) and warrants neuroimaging

Question 8

Spasmus Nutans Syndrome

Answer 8

1. Childhood nystagmus acquired in 1st year of life and spontaneously improves 2-8 years later
2. Asymmetric, small amplitude, high frequency, shimmering eye movements accompanied by head nodding and torticollis (abnormal head posture), may be monocular or binocular, ampitude and slow/fast phase may vary between eyes over course of a few seconds, variable or intermittent, horizontal, vertical or oblique may increase in abducted eye during lateral gaze
3. Head nodding or torticollis seen in 60% of patients and dampens nystagms and improves vision
4. Secondary strabismus and amblyopia may occur in more involved eye
5. Familial sometimes, associated with AA, Hispanics, low SES
6. Distinguished from infantile nystagmus by asymmetry, monocular, high-frequency, small amplitude, shimmering, multiplanar, variable nature of nystagmus Vs Infantile nystagmus consists of larger amplitude, lower frequency, bilateral, conjugate, symmetric, horizontal, constant
7. Etiology unknown
   
   1. Chiasmal/suprachiasmal tumors (gliomas)
   2. Retinal dystrophies (CSNB)
   3. Neurodegenerative disorders (Leigh disease, Pelizaeus-Merzbacher)
8. Neuroimaging indicated to exclude glioma or parasellar or hypothalamic tumors (above optic chiasm)
9. ERG should be done if signs of retinal dystrophy → progressive visual loss, photophobia, nyctalopia, eye pressing, paradoxical pupils, high refractive error
10. Progressive developmental delay → requires evaluation for neurodegenerative disease
11. Patient should be monitored and treated for associated amblyopia, strabismus
12. Abnormal head movements usually disappear after several years
13. Lack of resolution or development of neurological problems should prompt appropriate evaluation including neuroimaging

Question 9

Gaze-Evoked Nystagmus

Answer 9

1. Due to inability to maintain fixation in eccentric gaze → eyes shifts back to midline due to elastic properties of orbit and then corrective saccade (fast phase) back to eccentric target. Fast phase in direction of gaze. Amplitude of nystagmus increases as eyes moved in direction of fast phase = Alexander’s law which states that nystagmus increases in intensity (amplitude and frequency) as eyes moved in direction of fast phase
   
   1. Few beats of symmetric, low-frequency, small amplitude jerk nystagmus at extremes of far horizontal gaze without EOM dysfunction
2. Most commonly caused by dysfunction of neural integrator which ensures level of neural activity adequate to maintain eyes in eccentric position of gaze and against elastic forces of orbit
   
   1. Horizontal gaze neural integrator → nucleus prepositus hypoglossi
   2. Vertical gaze neural integrator → interstitial nucleus of Cajal
   3. Cerebellum with some neural integration
3. Pathologic gaze-evoked nystagmus → sustained, large amplitude, asymmetric should prompt evaluation including neuroimaging
   
   1. 2 most common etiologies:
      
      1. Toxic effects from drugs and medications (alcohol, sedatives, anticonvulsants, antidepressants
      2. Cerebellar disease → stroke, demyelination, tumor
   2. Myopathies of EOMs and MG may cause gaze-evoked nystagmus with similar pattern to CNS lesions

Question 10

Rebound Nystagmus

Answer 10

1. Seen in some patients with gaze-evoked nystagmus and often a manifestation of cerebellar disease
2. Prolonged eccentric gaze (>30 seconds) reduces amplitude of nystagmus → patient resumes central gaze and develops a jerk nystagmus with slow phase toward direction of initial eccentric gaze followed by fast phase saccade to center due to residual tonic innervation

Question 11

Peripheral Vestibular Nystagmus

Answer 11

1. Sometimes present with sudden, dramatic onset of disequilibrium with vertigo, nausea, vomiting
2. Symptoms worsened by particular head movements or postures. May have oscillopsia, tinnitus, hearing loss
3. After acute phase of peripheral vestibular loss that lasts days, patients experience slow period of gradually waning symptoms. Patients may have exacerbation years later when vestibular system challenged from fast-moving car or boat for example
4. From dysfunction of semicircular canals, otolithic structures, vestibular nerve → disrupts normally symmetric vestibular input to ocular motor nuclei. Toxicity usually bilateral.
   
   1. Asymmetric input from semicircular canals generates peripheral vestibular nystagmus. Peripheral vestibular nystagmus reflects combined effects of decreased afferent input from ALL 3 semicircular canals.
   2. Horizontal semicircular canals → to contralateral abducens nucleus and contralateral horizontal gaze. Lesion of horizontal semicircular canal results in slow phase (tonic phase) towards side lesion and fast saccade (jerk nystagmus) away from side lesion (nystagmus beats away from lesion).
   3. Anterior and Posterior canals → upgaze and downgaze respectively as well as contralateral torsion. Unilateral lesion of anterior AND posterior canals on one side has no effect on vertical gaze as both damaged. However, will see slow ipsilateral torsion with correctional saccade away from side of lesion.
   4. Thus, unilateral peripheral vestibular lesion generates horizontal and torsional nystagmus with jerk phases (fast phase) away from side of lesion. Alexander law = nystagmus more pronounced when gaze directed toward side of fast-beating component
5. Asymmetric otolithic component → skew deviation or ocular tilt reaction
6. Characteristic feature → Visual fixation dampens nystagmus
7. Enhancing nystagmus may be done by vigorous head shaking, hyperventilation, mastoid vibration, Valsalva maneuver
8. 4 clinical patterns of peripheral vestibular dysfunction often with nystagmus
   
   1. Vestibular neuronitis → acute monophasic disorder
   2. Meniere disease → recurrent vestibular dysfunction associated with tinnitus and hearing loss, progressive but with long symptom-free intervals
   3. Benign paroxysmal positional vertigo → due to free movement of otoconia particles (calcium carbonate crystals normally within utricle and saccule). Dix-Hallpike → head turned 45 degrees right or left and lowered below horizontal used to determine which side of semicircular canals dysfunctional. Epley maneuver to remove otoconia from semicircular canal
   4. Toxicity → aminoglycosides, chemotherapeutics. Usually no nystagmus but produces head-movement related oscillopsia and decreased vestibular ocular reflex
9. Cerebellopontine angle tumor → vestibular schwannoma or meningioma may produces Bruns nystamus = combination of gaze-evoked and peripheral vestibular nystagmus

Question 12

Central Vestibular Nystagmus

Answer 12

1. Often involves pathways governed by anterior, posterior semicircular canals INDIVIDUALLY or BOTH → Isolated vertical or torsional nystagmus common unlike peripheral vestibular nystagmus (horizontal and torsional with no vertical nystagmus from concomitant anterior and posterior semicircular involvement)
2. If central vestibular nystagmus of small amplitude and present outside primary position then patients may have no visual symptoms

Question 13

Downbeat Nystagmus

Answer 13

1. Most common form of central vestibular nystagmus
2. Upward drift of eyes followed by downward saccade
3. Lesions compromise vestibulocerebellum (nodulus, uvula, flocculus, paraflocculu) and diminish output from posterior semicircular canals to ocular motor neurons
4. Patients usually report oscillopsia that can be debilitating
5. Structural lesion may be associated and usually at cervicomedullary junction
6. Arnold-Chiari type 1 most common structural lesion → posterior fossa crowding and cerebellar tonsillar protrusion into foramen magnum
7. Antibodies to glutamic acid decarboxylase (GAD) have been identified in blood → cause downbeat nystagmus by interfering with GABAergic neurons of vestibular complex that normally inhibits flocculus
8. DDX
   
   1. Arnold-Chiari type 1
   2. Syrinx
   3. Platybasia (flat skull base)
   4. Foramen Magnum tumors
   5. Demyelination
   6. Stroke
   7. Spinocerebellar degenerations
   8. Brainstem encephalitis
   9. Paraneoplastic syndrome
   10. GAD ab
   11. Drug toxicity (lithium, anticonvulsants)
   12. Impaired nutrition (Wernicke, paracentral feeding, Mg deficiency)
   13. Idiopathic’
9. Treatments → clonazepam (GABA agonist), baclofen, gabapentin, memantine, amifapridine, base-out prisms to induce convergence and may improve oscillopsia associated with downbeat nystagmus

Question 14

Upbeat Nystagmus

Answer 14

1. Downward drifting followed by corrective saccade upwards
2. Lesions in brainstem often medulla or other areas of posterior fossa
3. Demyelination, stroke, cerebellar degeneration, tobacco smoking

Question 15

Torsional Nystagmus

Answer 15

1. From peripheral vestibular nystagmus with also horizontal nystagmus
2. Pure torsional nystagmus → indicative of central etiology usualy medullary lesion

Question 16

Periodic Alternating Nystagmus

Answer 16

1. Strictly horizontal and that oscillates predictably in direction, amplitude and frequency
2. Nystagmus toward one side progresses in ampliude and ffrequency up to a certain point then has no nystagmus → nystagmus reverses direction that leads to crescendo then decrescendo and stops.
3. Congenital or Acquired
4. Acquired form → oscillation cycle of 2-4 minutes
5. for any horizontal nystagmus that occurs in primary position should be observed for at least 2 minutes to be certain not PAN
6. Patient may also exhibit head turn towards direction of nystagmus to minimize nystagmus per Alexander’s law
7. Due to unstable velocity storage → Prolonged vestibular-ocular response due to vestibulocerebellar disease.
   
   1. Arnold-chiary Type 1
   2. Cerebellar degeneration
   3. MS
   4. Cerebellar tumors
   5. Stroke
   6. Anticonvulsant medication
   7. Bilateral loss of vision → if reversed (clearing of VH) then PAN may be abolished
8. Tx → baclofen (GABA agonist) may be able to abolish acquired form

Question 17

Acquired Pendular Nystagmus

Answer 17

1. Acquired → Pendular, slow-phase, horizontal, vertical, torsional. If both verticla and horizontal then oblique nystagmus if in phasae or elliptical nystagmus if out of phase. Conjugate or disconjugate and often dissociated
2. Congenital → only horizontal movements
3. Seen in MS patients, blindness due to optic nerve disease
4. Typically worse in eye with poorer vision
5. Monocular or binocular
6. Memantine or gabapentin may reduce severity and improve vision, unilateral retrobulbar botulinum toxin type A reduces amplitude of nystagmus and may improve vision
7. Total cessation of eye movements may cause more blurred vision when walking due to loss of normal VOR that adjusts eye position as head moves
8. Acquired pendular nystagmus may accompany palatal myoclonus → acquired oscillation of palate. Eye movements continuous, rhythmic, 1 Hz frequency, conjugate in vertical plane, persist during sleep. May also see synchronous movements of facial muscles, pharynx, tongue, diaphragm, trunk, extremities.
   
   1. Usually arises months to years after lesion involving area of red nucleus, inferior olivary nucleus, contralateral cerebellar nuclei

Question 18

See-Saw Nystagmus

Answer 18

1. 1 eye elevates and intorts while 1 other eye depresses and extorts → disjunctive
2. Typically pendular, slow, similar amplitude in each eye though amplitude may be larger in eye with poorer vision
3. Congenital or Acquired
4. Lesions of chiasm, midbrain, trauma, parasellar-diencephalic tumors such as craniopharyngioma frequent causes, hydrocephalus, congenital achiasma
5. Bitemporal hemianopia may be seen
6. May be seen in patients with RP, albinism, optic nerve hypoplasia

Question 19

INO Nystagmus

Answer 19

1. Nystagmus of abducting eye occurs when gaze directed to opposite side of lesion
2. Due to increased neural pulsing to overcome adduction weakness
3. Due to Hering’s Law → increased neural signaling also delivered to contralateral yoke muscle (LR) causing excessive saccadic movements

Question 20

Voluntary Flutter

Answer 20

1. Rapidly oscillating eye movements almost always horizontal that can be induced volitionally
2. Lack slow phase thus not a form of nystagmus, appear as high frequency, conjugate, back-back saccades without intersaccadic interval
3. Associated with convergence, facial grimacing, eyelid fluttering
4. Rarely longer than 30 seconds
5. Ocular flutter different → sustained, associated with neurological signs (ataxia, ocular dysmetria, mycoclonus), no convergence or facial grimacing or eyelid fluttering

Question 21

Convergence-Retraction Nystagmus

Answer 21

1. Not really nystagmus as NO slow phase
2. Due to co-contraction of ALL EOMs on attempted upgaze
3. MR most powerful and contraction produces convergent movements even when all other EOMs are contracting → co-contraction of all EOMs causes retraction of globe.
4. Convergence-retraction nystagmus → Lesion in Dorsal Midbrain
   
   1. Associated with paresis of upgaze, pupillary light near dissociation, skew deviation, bilateral eyelid retraction (Collier sign)
   2. Best demonstrated by having patient attempt upward saccade or by following downward-rotating OKN drum

Question 22

Superior Oblique Myokymia

Answer 22

1. Monocular, paroxysmal, high-frequency bursts of SO muscle contraction. Last for few seconds, occur numerous times per day and produce vertical and torsional movements. Small amplitude and require magnification (20D lens) to see them.
2. Can use SLE to focus on conjunctival vessel to help identify movements
3. Patients may experience oscillopsia, vertical/torsional diplopia, blurry vision, tremulous ocular sensations
4. Spontaneously or after downward eye movement or blinking
5. May occur when superior cerebellar or posterior cerebral artery compresses CN 4 root exit zone. May occur prior to or after CN 4 palsy or from aberrant regeneration
6. May be associated with MS, posterior fossa tumor, stroke, trauma in rare cases and neuroimaging may be considered
7. May recover spontaneously or treatment with B-blockers (topical, systemic), carbamezapine, phenytoin, baclofen, gabapentin. May need to decompress CN 4 rarely

Question 23

Oculomasticatory Myorhythmia

Answer 23

1. Pendular vergence oscillations that occur with contractions of masticatory muscles → vertical saccadic palsy may be seen in Whipple disease
   
   1. May also see diarrhea, fever, weight loss, lymphadenopathy, cognitive dysfunction
   2. Dx with duodenal bx using PAS to document Tropheryma whipplei or by PCR
   3. May be curable with antibiotic therapy