Thread by @MDCearns

Everyone needs a distraction at the moment. Some time ago I was asked to discuss and demystify #nystagmus - when does it reflect a concerning pathology? Being in isolation with Covid, now seemed time to take on the challenge! An ‘eye-boggling’ #tweetorial. #meded #neurotwitter 🧵

Understanding nystagmus really means understanding how eye movements (EMs) are controlled. (This is what makes it interesting - so don’t give up on me yet!) Here’s a whistle-stop tour of how the brain controls something integral to your everyday function...

CN VI turns the eye out, whilst III turns it in (with III and IV controlling up and down). The eyes need to move in perfect unison, and so they are ‘yoked’ by a tract called the MLF. This connects the nucleus of VI (out) on one side with III (in) on the other, to enable this:

There are different types of EM. Saccades are the jerky movements that allow us to quickly scan our large visual field and find what we're looking for. Pursuits are the smooth movements that allow us to follow a moving object, keeping it on exactly the same part of the retina.

These are controlled in the brainstem. 'Pause' neurons keep the eyes still, for fixed gaze. 'Burst' neurons override these just long enough to produce the saccade. Horizontal burst neurons are in the pontine reticular formation; vertical ones are in the midbrain, near the tectum.

Horizontal burst neurons in the PPRF connect to the VI nucleus on the same side (also in the pons, naturally), which connects to the contralateral III via the MLF. The result: the right side of the pons looks right, and vice versa (green arrows).

But we have voluntary control of EMs! This is mostly from the 'frontal eye fields'. Like other motor fibres from the frontal lobe, these cross over - to control the contralateral PPRF. The result: the right side of the brain looks left, and vice versa (red lines).

(Just while we’re here, this is why major frontal lobe pathologies cause contralateral weakness and ipsilateral gaze deviation, or ‘looking away from the weak side’ - because the frontal eye field activity is also lost. Frontal overactive from seizure can cause the opposite).

The cerebellum refines precision through 'muscle memory'. But precise EMs would be useless if head position wasn't taken into account - so proprioceptive information from the neck muscles and balance from the inner ear also feed in. This is key for understanding nystagmus.

Fix your eyes on an object, and turn your head slowly to the right keeping that gaze. You’ll notice that in response, your eyes have to turn equally to the left to keep the object perfectly still. These are vestibulo-ocular movements, and what the inner ear does for a living.

Here's how. As the head turns right (black arrows), the fluid inside the lateral semicircular canal in the right inner ear is displaced medially (red arrow) - where it stimulates the crista (sense organ that makes the vestibular nerve fire, activating the vestibular nucleus).

The right vestibular nucleus projects to the left VI (which, as we know, projects to the right III via the MLF). The result: when the head turns right, the eyes turn left. Ingenious! 👏 (N.B. the opposite happens simultaneously on the left - reverse fluid movement, deactivation).

(Just while we're here, this is how brainstem 'caloric' testing works. The cold water in the right ear cools down the semicircular canal, and fluid moves away from the sense organ by convection, so the eyes deviate to the left. The reverse happens with warm water).

OK - that's the painful tweets. Nystagmus: there's typically a fast ‘jerk’ phase and a slow ‘drift’ phase back towards the central position. It’s normally said to ‘beat’ in the direction of the fast phase - but in reality, the pathology is in the direction of the slow phase!

Why? The eyes shouldn’t move slowly and smoothly unless they are following an object, i.e. a pursuit! So the ‘drift’ is abnormal - and the the fast component is a saccade, which is a normal response to counteract the drift.

This explains how to make a nystagmus more clinically apparent - it should be exacerbated by looking into the direction of the beat of nystagmus. This exaggerates the abnormal drift back to the central position, making the corrective saccade bigger and easier to spot.

This gets called ‘gaze-evoked’ - nystagmus in a given direction of gaze. Most people have a few beats of this at the very extremes of gaze, as the extraocular muscles struggle to turn the eye further than it wants to - this is normal.

In the same way, ANY weakness of a particular eye movement (e.g. weakness of abduction in VI palsy, weakness of adduction in internuclear ophthalmoplegia, specific extraocular muscle weakness) can cause nystagmus in the ‘good’ eye on looking into the direction of weakness.

One of the key clinical scenarios that demands an understanding of nystagmus is the patient with vertigo. Vertigo can have 'peripheral' causes affecting the inner ear or nerve, or concerning 'central' causes like brainstem tumour/vascular/inflammatory disease. Which is which?

Peripheral disease like Meniere’s, BPPV and vestibular neuritis acts like the cold water in the ear - deactivating the vestibular nucleus, causing the eyes to deviate or drift towards the affected side. So the nystagmus beats to the OPPOSITE side to counteract this.

So in the Dix-Hallpike test, BPPV causes the eyes to beat towards the floor. There can be a rotary component due to involvement of other semicircular canals - but should only ever be in one direction. If you repeat immediately, there'll be a refractory period with no nystagmus.

(Note - the patient will not thank you for doing the Dix-Hallpike test more than once!)

If the vertigo patient has any vertical or multidirectional component to their nystagmus, be suspicious of a central vestibular problem. On Dix-Hallpike, these patients may get nystagmus in either direction, with no refractory period, and associated with vomiting.

Vertical nystagmus is always central in origin. Typically, upbeat nystagmus comes from cerebellar midline vermis lesions; downbeat from the cervicomedullary junction and lowest part of the vermis (such as Chiari malformations). 🧠

In cerebellar disease, the eyes may briefly oscillate around an object before settling on it. This is a form of dysmetria of the eyes - exactly like intention tremor. They can also get horizontal gaze-evoked nystagmus towards the lesion (opposite to peripheral vestibular).

Because of all this, central lesions often cause mixed horizontal, vertical and rotary effects. Finally and importantly - let's not forget that drugs are a common cause of all of the above - a side-effect in particular of sedatives, anticonvulsants and alcohol.💊💉🍷

Nystagmus is a complex topic to try to summarise (let alone make entertaining!) and there are other rarer forms and causes not included here. I hope it helps. Final note - have a happy Christmas and don't drink yourself into a gaze-evoked nystagmus! 🎄🙏