Understanding nystagmus and approaching nystagmus is often difficult and confusing, most probably because the pathophysiology for nystagmus is not clearly defined and there is no pathognomonic nystagmus sign that could lead to a single diagnosis. In fact, there is an exhaustive list of diseases for a single nystagmus finding[ref1]. However, it does not mean that we cannot narrow down our diagnoses; by the existence of postulated hypothesis for the pathophysiology of nystagmus, we can somehow localize the lesion.
Nystagmus is defined as an involuntary to-and-fro oscillatory movement of the eyeballs[ref2]. Nystagmus is named by its direction of fast phase. If the fast phase is toward the left, then it is named left horizontal nystagmus. If the fast phase is upwardly, then it is named upbeat nystagmus[ref2][ref3]. The slow phase is, generally, the “pathological” incident while the fast phase represents the corrective re-compensation.
In approaching nystagmus, we will have to classify it accordingly. It can be classified into[ref2][ref3[ref4]:
1. Physiological or pathological
2. Acquired or congenital
3. Monoocular or biocular
4. In terms of direction: Horizontal or vertical (upbeat or downbeat) or torsional; or multidirectional
5. In terms of waveform: Jerk (which has a fast and slow phase) or Pendular (more or less equal velocity and amplitude)
6. Gaze-evoked or not gaze-evoked.
Additional factors that aid your diagnosis:
1. Relieved or not relieved by visual fixation
2. Additional symptoms and signs
3. Special character (discussed below)
The most important step is to know whether a nystagmus is pathological, central or peripheral, and the recognition of waveform that might help you localise the area of lesion. Now let’s look into the details. [ref1][ref2][ref4][ref5][ref6].
A) Physiological or Pathological
Physiological causes of nystagmus include optokinetic nystagmus (occurs for eg., you are looking at the trees in a moving car), vestibular stimulation (such as a caloric test), and nystagmus that occurs at extreme gaze. Physiological causes are not easily missed, they are often temporary and seldom a complaint.
B) Monoocular or biocular
Most nystagmuses are biocular unless in a medial pontine stroke, where the unilateral medial longitudinal fasciculus is affected. Patient will present with contralateral internuclear opthalmoplegia (INO). If the right medial longitudinal fasciculus is damaged, and patient is instructed to look to the right, the left eye will not look to the right while the right eye has horizontal nystagmus. This is because the medial longitudinal fasciculus function is for concurrence contraction of medial rectus muscle and lateral rectus muscle on adduction gaze. Any lesion that damages the unilateral medial longitudinal fasciculus can produce INO.
B) Central or peripheral.
Central causes of nystagmus are often pendular, do not have a fast-slow phase, and is vertical in direction; even though horizontal and jerk nystagmus can occur with central lesions. Peripheral origin of nystagmus typically present as a horizontal and jerk nystagmus. In a peripheral lesion, jerk nystagmus has its fast phase beating away from the side of lesion while central lesion has its fast phase beating towards the side of lesion. It is difficult to use this factor to differentiate between central and peripheral vestibular lesions because you do not know which side the lesion is in the first place. A better way to do so is by fixing the gaze and see if nystagmus is reduced or relieved. In peripheral nystagmus, it is often relieved by gaze-fixation while central nystagmus is not. Another important differentiating clue is the associative sign and symptoms; including cerebellar sign such as ataxia, dysdiadokinesia, intention tremor, and scanning speech; and brainstem sign such as bulbar palsy, hemiplegia, or unilateral sensory loss. But this may not be enough, central lesion can be cerebellar, brainstem, posterior hemisphere and cerebral hemisphere. Below is table for differentiating central and peripheral:
C) Acquired or congenital
Congenital is not difficult to be differentiated from acquired; mainly by age. Congenital nystagmus is usually horizontal, pendular type, and become worse with fixation. It is sometimes associated with albinism and blindness. However, similar presentation occurred with acquired disease too, thus age is the better differentiating factor.
Perhaps the most important step is the recognition of the waveform. It is important to understand some postulated theories and hypothesis on these waveform, as this could result in easier remembering of the link between the waveform and site of lesion.
In vertical beats, there is upbeat and downbeat. Upbeat nystagmus is due to pontine lesion which result from the damage of ventral tegmental tract (VTT) originating from the superior vestibular nucleus(SVN). This tract course through the ventral pons and transmitting excitatory upward vestibular signals to the 3rd (oculumotor) nerve nucleus. Thus any lesion that disturbed this pathway could result in upbeat nystagmus. In addition, similar nystagmus is produced from lesion of caudal medulla. Interestingly, there is no clinical case of downbeat nystagmus caused by focal lesion of the brainstem. Downbeat nystagmus is usually caused by lesion of cerebellar flocculus, which in turn resulting in disinhibition of SVN-VTT pathway, followed by relative hyperactivity which drive the upward slow-phase. Downbeat nystagmus are seen in structural lesion of the cervicomedullary junction such as Chiari-malformation. Other possible causes include any form of lesion to cerebellar flocculus. [ref7]
Before going into pendular nystagmus, let’s review some relevant information. Nystagmus invariably occurred in total blindness. When the eyes is unable to fix a vision for example in a sudden dark room, there will an attempt to fix in a previously remembered location. If this response mechanism is disrupted, as in the case of lesion to the optic nerve (optic neuritis or multiple sclerosis), there will be pendular nystagmus. This also explains the presence of pendular nystagmus in congenital blindness. However, lesion of the cortico-pontine-cerebellar or olivocerebellar pathway could yield similar pendular nystagmus. Thus showing the hypothesis is incomplete and pendular nystagmus has a wide range of causes. [ref8]
In gaze-evoked nystagmus, there is also subdivision into vertical and horizontal. Not much is known about its pathophysiology but is stated that it is dues the lesion of the neural integrator function located in the brainstem, specifically nucleus prepositus hypoglossi (at medulla) for horizontal integrator and interstitial nucleus of Cajal (upper midbrain) for vertical. Damaged involving these area will give rise to gaze-evoked nystagmus of respective direction. Similar presentation could occur in corresponding vestibulocerebellar pathway lesion. [ref9]
See-saw nystagmus is usually associated with parasellar lesions such as pituitary tumour, or any lesion to the optic chiasm. See-saw nystagmus has been reported in visual loss dues to retinitis pigmentosa. [ref8]
Periodic alternating nystagmus (PAN), presented as horizontal (almost always) nystagmus, then stopped and followed by reverses direction of the nystagmus; this cycle is repeated usually every minute. The presumed mechanism is damage to the vestibulo-ocular tract at the pontomedullary junction; usually a cerebellar lesion or brainstem lesion. Hence, it is also has a wide range of causes.
Convergence-retraction nystagmus, perhaps the most “pathognomonic” of all type of waveform, presented as adducting saccades (medial rectus contraction). This can occurred spontaneously or during an attempted upward gaze (often accompanied by retraction of the eyes into orbits). This typically points toward mesencephalic pretectal region (dorsal midbrain) lesion, usually a compressing pinealoma.
Below is the table for summary of waveform of nystagmus.
As you may have noticed, some waveform has no distinct localizing value, but with the aids of associative symptoms, narrowing down diagnosis is possible. Below is the suggested algorithm for the approach of nystagmus based on it’s waveform. The author suggests that the best localizing method is by looking for the associated sign and symptoms as nystagmus characteristic although suggestive, may not be discriminative.
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