Saccades are rapid, binocular, conjugate eye movements that bring visual targets onto the fovea, occurring about 3 times per second between fixations.
Saccadic intrusions are involuntary conjugate saccades that interrupt fixation. Unlike nystagmus, which is triggered by a slow drift, saccadic intrusions are triggered by the saccade itself 2). They are classified as square-wave oscillations when there is an intersaccadic interval (ISI) between consecutive abnormal eye movements, and sine-wave oscillations when there is no ISI.
Saccades are generated by a pulse-step mechanism. High-frequency burst firing from burst neurons (pulse) provides the eye position signal via tonic neurons (step), and is inhibited and controlled by pause neurons (OPN). Disruption of this local neural circuit leads to saccadic intrusions.
A few intermittent SWJs can be seen in healthy individuals, but persistent saccadic intrusions such as ocular flutter and opsoclonus are pathological and require evaluation.
QHow do saccadic intrusions differ from nystagmus?
A
Nystagmus is rhythmic and regular, initiated by a slow drift with a fast corrective phase. Saccadic intrusions are triggered by the saccade itself, are non-rhythmic, intermittent, and non-sustained. When clinical distinction is difficult, eye movement recording (video-oculography) is necessary 2).
Saccadic intrusions are broadly classified by the presence or absence of an intersaccadic interval (ISI).
Type with ISI (Square-wave oscillations)
Square-wave jerks (SWJ): Amplitude 0.5–5° (typically <2°), ISI ~200 ms. Double horizontal saccades. Common in elderly, PD, MS, PSP.
Macro square-wave jerks (macro SWJ): Amplitude 5–15°, pause duration ~0.1 s. Seen in cerebellar disease, PSP, MS.
Square-wave pulses (SWP): Similar to SWJ but with shorter ISI and larger amplitude. Almost always associated with MS, PSP, MSA.
Macrosaccadic oscillations (MSO): Induced by gaze shifts. Horizontal saccades with increasing and decreasing amplitude. Due to lesions of the cerebellar fastigial nucleus or outflow pathways.
Saccadic pulses (SP): Brief saccades away from the target followed by rapid refixation. Common in MS, trauma.
Type without ISI (Sinusoidal oscillations)
Ocular flutter: Horizontal conjugate saccades with amplitude 1–5°, frequency 10–25 Hz. Triggered by blinks or voluntary eye movements. Dysfunction of PPRF or cerebellar fastigial nucleus.
Opsoclonus: Multidirectional saccades with vertical and torsional components, unlike ocular flutter. No ISI. Widespread brainstem and cerebellar dysfunction. Associated with ataxia and myoclonus.
QIf square-wave jerks (SWJ) are found, does it always indicate disease?
A
A few intermittent SWJs can be observed even in healthy individuals and the elderly. However, frequent SWJs, those with an amplitude exceeding 5°, multidirectional or disconjugate SWJs suggest neurological disorders such as PSP or cerebellar disease, and require further examination.
Eye movement examination: ocular misalignment, nystagmus, smooth pursuit, vestibulo-ocular reflex (VOR), optokinetic nystagmus (OKN), head impulse test (HIT), conjugate movements, and vergence movements
Cover/uncover test: performed at both near and far distances in primary position and diagnostic positions of gaze
Video-oculography: necessary for detecting subtle findings. High-speed eye tracking is recommended 2)
Electro-oculography (EOG): two-dimensional (horizontal and vertical) recording is desirable, and three-dimensional recording including torsion is preferred. Parameters to evaluate: visually guided saccades (latency and amplitude), pursuit (gain), VOR (gain), and fixation (nystagmus waveform analysis, square wave jerk latency, slow phase waveform of sawtooth nystagmus)
The goal is to reduce or eliminate abnormal eye movements without interfering with physiological saccades and gaze holding. The principle of treatment is to target the underlying disease.
For vertical nystagmus, periodic alternating nystagmus, and saccadic intrusions, GABA_B agonists, which are inhibitory neurotransmitters in the cerebellum, may be highly effective.
Baclofen (Gabarone tablets 5 mg, 3–6 tablets, divided into 1–3 doses): GABA_B agonist. Useful for cerebellar eye movement disorders.
Prism glasses: If gaze-dependent nystagmus is present, adding the same prism power to both eyes with the base in the direction that worsens the nystagmus may reduce oscillopsia in primary gaze.
If the underlying disease is clear, proceed with its treatment. If untreatable, aim to reduce oscillopsia and improve visual information intake.
Deep brain stimulation (DBS): Improvement has been reported in SWJ due to PD settings and other causes.
QWhich department provides treatment for saccadic intrusions?
A
Depending on the underlying disease, neuro-ophthalmology or neurology is the main specialty. If paraneoplastic syndrome is suspected, collaboration with oncology is necessary. In pediatric cases, pediatric neurology is also involved. Detailed examination at a specialized facility and multidisciplinary collaboration are important.
During fixation, OPNs fire and inhibit BNs. Before saccade initiation, the inhibitory center in the superior colliculus switches, reducing OPN→BN inhibition and increasing BN→OPN inhibition, allowing the saccade to be executed. This local neural circuit is located in the brainstem and is controlled by higher centers in the cerebrum (frontal and parietal lobes), thalamus, basal ganglia, superior colliculus, and cerebellum.
The exact mechanism is unknown and depends on the underlying disease, but the following hypotheses have been proposed.
BN membrane property change hypothesis: Changes in BN membrane properties disrupt the balance of excitation and inhibition during physiological saccades.
Higher center inhibitory dysfunction theory: Dysfunction of the basal ganglia, cerebellum, cerebral hemispheres, and superior colliculus leads to a state where omnipause neurons (OPN) cannot be strengthened.
Immune-mediated theory: Association with immune-mediated mechanisms involving B cells and T cells.
The presumed lesion sites for each type are as follows2):
SWJ: Cerebellar vermis or OPN dysfunction
MSO: Fastigial nucleus/cerebellar vermis lesion
SP: Instability of the gaze-holding system (pontine/medullary burst neuron failure)
Ocular flutter: Disinhibition of brainstem reticular formation/saccadic burst neurons
Opsoclonus: Breakdown of OPN inhibition from the cerebellum/brainstem
7. Latest Research and Future Perspectives (Research-stage Reports)
Dai & Kuwera (2022) reported a case of a 9-month-old infant with non-accidental trauma (NAT) where ocular flutter was the presenting sign1). Bilateral supratentorial subdural hematomas and cortical venous thrombosis were found, and they noted that the threshold for imaging should be kept low when NAT is suspected. It has also been reported that preterm infants have impaired voluntary saccade control (especially inhibitory control of antisaccades) compared to full-term infants, with a higher frequency of intrusive saccades during smooth pursuit.
Ocular flutter and seesaw nystagmus remain difficult to treat, and further research is needed2). Prognosis depends largely on the underlying disease.
Pediatric opsoclonus-myoclonus syndrome associated with neuroblastoma: Approximately 80% have neurological sequelae. Poor prognosis.
Adult idiopathic opsoclonus-myoclonus syndrome: Usually monophasic with good prognosis.
QWhat is the prognosis of opsoclonus-myoclonus syndrome?
A
In pediatric opsoclonus-myoclonus syndrome associated with neuroblastoma, approximately 80% have neurological sequelae and the prognosis is considered poor. On the other hand, adult idiopathic opsoclonus-myoclonus syndrome is usually monophasic and the prognosis is relatively good. Early diagnosis and treatment are important in both cases.
Dai X, Kuwera E. Saccadic intrusions in pediatric non-accidental trauma. Am J Ophthalmol Case Reports. 2022;26:101564.
Gurnani B, et al. Nystagmus: A Comprehensive Review of Etiology, Classification, Diagnostic Work-Up, and Management. Clin Ophthalmol. 2025;19:1617-1653.
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