Introduction

Multiple sclerosis (MS) is a chronic autoimmune and inflammatory disorder that affects the central nervous system (CNS). It destroys the myelin that covers the neurons' axons. The progression of MS varies significantly from one patient to another. In most cases, the disease starts with episodes of reversible neurological deficits, which are frequently followed by a gradual and progressive decline in neurological function.¹

MS is the most common non-traumatic disability in young adults. The incidence of multiple sclerosis is increasing, but the cause is still unclear.² It appears to be related to a combination of genetic susceptibility and a trigger factor - such as a virus, metabolic issues, or environmental factors - that together lead to the onset of a disease attacking the CNS.

Over 30% of people with MS have muscle stiffness, mainly in the legs. Early clinical signs of MS generally include sensory disturbances, such as paresthesias (numbness and tingling), dysesthesias (burning or “pins and needles”), double vision (diplopia), coordination problems (ataxia), vertigo and bladder trouble.¹

Vision problems are very common in MS patients and can seriously affect quality of life, often more than in people with other chronic conditions.³

MS often causes eye movement abnormalities due to inflammatory demyelinating lesions, especially when they affect the posterior fossa, leading to disorders like acquired pendular nystagmus (APN) and internuclear ophthalmoplegia (INO).⁴ These are the two most common types of nystagmus in MS, though other forms can occur depending on the location of the demyelinating plaques.⁵ 

What is nystagmus?

Nystagmus comes from the Greek words nustagmos (meaning nodding or drowsiness) and nystazein (meaning to be sleepy). It describes an oscillatory, uncontrolled, rapid movement of the eyes, which can be slow, fast or both. Nystagmus can be continuous, appear suddenly, or be triggered by changes in position of the head or gaze.⁶

Physiological nystagmus is the normal movement of eyes that happens when the body rotates or when we follow moving scenes with our eyes. It helps keep vision clear (this includes vestibular and optokinetic nystagmus). Pathological nystagmus, on the other hand, is abnormal. It causes the eyes to move away from the visual target, resulting invision problems.⁷

It is often the result of diseases that affect the cortex, brainstem, cerebellum, anterior visual tracts, or peripheral vestibular apparatus. Moreover, nystagmus can be: manifest (always present), latent (only when one eye is covered), or a mix of both.⁶

Causes of nystagmus in MS

Patients with MS may develop lesions in specific areas such as the medulla, cerebellar peduncles, posterior pontine tegmentum, or midbrain. The cerebellum and its connections are frequently affected in MS, leading to different types of nystagmus:

• Gaze-evoked nystagmus (GEN) happens when the eyes cannot maintain a side gaze due to damage of the neural integrator - a system involving the cerebellum that is responsible for stabilizing eye position
• Downbeat nystagmus (DBN) is due to loss of normal cerebellar control over vertical eye movements
• Central positional nystagmus (either downbeat or upbeat) manifests as vertigo caused by the movements of the head
• Periodic alternating nystagmus (PAN), a spontaneous horizontal eye movement where the fast phase changes direction about every 2 minutes

Demyelination and axonal damage in MS also frequently occurs in a key area of the brainstem called the medial longitudinal fasciculus (MLF). When the MLF is damaged, it causes internuclear ophthalmoparesis (INO), the most common eye movement disorder seen in MS.

Acquired pendular nystagmus (APN) is therefore a frequently observed form of nystagmus in individuals with multiple sclerosis. This type is believed to result from damage in the neural integrator network in the brainstem and cerebellum. Lesions that lead to APN are frequent in the paramedian tract (PMT) cell groups. When these cells are damaged, they cannot stabilize eye movements properly, leading to the oscillations typical of APN.⁴

Clinical presentation

Some of the most common symptoms of nystagmus in patients with MS include:

• Involuntary eye movements 
• Vertigo (a spinning sensation)
• Oscillopsia (images moving side to side)⁸

• Fatigue
• Lightheadedness
• Dizziness
• Visual instability, especially when sitting upright⁹

Treatment strategies

The treatment of nystagmus is personalised and it is based on different factors, including the type of nystagmus, symptoms like oscillopsia, visual potential, and the null point location. The treatment approaches can be classified into pharmacological, optical and surgical treatments.¹⁰

Pharmacological treatment

Pharmacological treatments can help reduce abnormal eye movements, while preserving normal function. However, side effects often limit long-term use. GABA and glutamate play key roles in gaze control, thus drugs targeting these neurotransmitters have been investigated.¹⁰

Various pharmacological treatments have been employed to manage nystagmus. When secondary to MS, MRI localisation of lesions can help clarify the underlying pathophysiology and guide treatment.

Acquired pendular nystagmus, often due to instability in the neural integrator (NI) loop involving the paramedian tracts, may improve with drugs that stabilise NI cell membranes. Gabapentin and memantine, which modulate calcium channels and glutamate receptors respectively, indirectly depolarise NI structures like the nucleus prepositus hypoglossi by reducing GABAergic inhibition. Downbeat nystagmus (DBN), typically due to cerebellar flocculus lesions in MS, responds to oral clonazepam, baclofen, and gabapentin.

Potassium channel blockers such as 3,4-diaminopyridine (3,4-DAP) can reduce the velocity of abnormal eye movements. However, 4-aminopyridine (4-AP) can cross the blood–brain barrier more easily and helps restore the function of the neural integrator, which controls stable eye position, which is why it is more preferred. 4-AP has also been found to be effective in other types of nystagmus, including upbeat and central positional nystagmus.

Periodic alternating nystagmus can be treated with oral baclofen, whose therapeutic effect on the vestibular nuclei and vestibulocerebellum is likely mediated through GABAergic modulation.

Internuclear ophthalmoplegia may be treated with dalfampridine, which has shown improvements in horizontal saccades and visual quality in early studies.⁴

Optical treatment

An optical system that helps stabilise vision in people with nystagmus uses strong high plus spectacle lenses together with minus contact lenses. The spectacle lenses focus the image close to the centre of eye rotation, and the contact lens refocuses it onto the retina. Since the lens moves with the eye, the image stays more stable, reducing the visual disturbance caused by involuntary eye movements by up to 90%. However, this system has important limitations.

In fact, it disables normal eye movements, such as those for balance and depth perception, so it is only helpful when the person is sitting still and using one eye. It also narrows the field of view. For MS patients with tremors or ataxia, it can be difficult to insert the contact lens.

For these patients, a simpler version using soft lenses and offering milder image stabilisation might still be helpful, but only for simple tasks and short periods, like watching a TV show.¹¹

A newer method uses an electronic device to detect and cancel out the eye movements caused by nystagmus. It works best for pendular nystagmus, because the device can tell the difference between these abnormal movements and normal ones like quick eye shifts. The system uses special image-shifting lenses and is being developed as a small, battery-powered device.¹²

Surgical treatment

Surgery for nystagmus focuses on improving vision and head posture by adjusting the eye muscles. The goal is to shift and widen the “null point” (the eye position where nystagmus is least), correct abnormal head positions, or help reduce nystagmus in people whose symptoms improve when they cross their eyes (converge). This is done by weakening or strengthening the muscles that move the eyes to guide them into a better position¹⁰.

Key techniques include the Anderson-Kestenbaum procedure, which moves eye muscles to bring the null point into a straight-ahead gaze, and muscle recession, which weakens certain eye muscles to reduce movement. Another method, tenotomy and reattachment, involves detaching and reattaching the eye muscles at the same place, possibly altering feedback to the brain and helping stabilise gaze. These surgeries may benefit selected patients but require careful evaluation due to variable results.¹²

Botulinum toxin

Botulinum toxin can be used by injecting it into the eye muscles to temporarily reduce involuntary eye movements,although it often causes side effects such as ptosis and diplopia. It also weakens normal eye movements, which can cause blurry vision or oscillopsia when walking. It may help some people, especially if they have monocular vision, but its effects are temporary and limited.¹²

Summary

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system by disrupting the myelin leading to neurodegeneration. MS can cause various neurological problems, including eye disorders such as nystagmus,an involuntary eye movement, either normal or due to neurological damage.Common types in MS include acquired pendular nystagmus (APN), internuclear ophthalmoplegia (INO), and gaze-evoked nystagmus, caused by demyelinating lesions in different brain areas like the cerebellum, brainstem and medial longitudinal fasciculus (MLF).
Treatment of nystagmus can follow pharmacological, optical or surgical approaches. Drugs act on neural circuits that control eye stability, but their benefits are often limited by side effects. Optical strategies, such as special lens systems, aim to stabilise images on the retina but restrict normal vision and are only suitable in specific situations.
Surgical options focus on repositioning or weakening eye muscles to shift the null point and improve visual function or head posture. Techniques like the Anderson-Kestenbaum procedure and tenotomy with reattachment may help in selected cases. Botulinum toxin injections offer short-term relief but come with important side effects. Overall, treatment aims to reduce symptoms and improve visual stability.