Multiple Sclerosis

Multiple sclerosis is a long-term disease in which the body's own immune system mistakenly attacks the insulating coverings of nerve fibres (myelin) in the brain and spinal cord. The damaged areas — called "plaques" or "lesions" — interfere with the nerves' ability to carry signals quickly. Symptoms depend on exactly where in the brain or spinal cord the lesions form, and can include weakness, numbness, vision problems, balance problems, and dizziness.

Vertigo is the first symptom in roughly 5% of patients, and occurs at some point in around 50% of patients across the disease course. The vertigo is usually a sign that the brainstem (the part of the brain that connects to the spinal cord) has been involved. In a young person — particularly a young woman — sudden vertigo with double vision is one of the classic presentations that triggers the suspicion of MS.

Modern MS treatment is highly effective. Once the diagnosis is established by MRI, lumbar puncture, and the clinical pattern, disease-modifying therapies can dramatically reduce relapse frequency and slow disability accumulation. Specific vestibular symptoms are managed in parallel — with medications during attacks, with vestibular rehabilitation between attacks.

Multiple sclerosis is the most common chronic inflammatory disease of the central nervous system, affecting 2.5–3 million people worldwide. Peak onset is in the third decade, with a female-to-male ratio of around 3:1 in relapsing-remitting disease.1 Geographical gradients — higher incidence at higher latitudes — and family-history clustering support a combination of genetic susceptibility and environmental triggers (vitamin D status, Epstein-Barr virus, smoking).

Vestibular and oculomotor symptoms are common across the disease course. Vertigo presents as the index symptom in approximately 5–10% of MS patients and occurs at some point in around 50%.5Three patterns recur: isolated central vestibular syndromes from brainstem plaques, oculomotor abnormalities (most distinctively INO), and chronic disequilibrium from cumulative cerebellar or brainstem involvement. Vertigo in MS is almost always central — peripheral vestibular symptoms in a known MS patient should prompt the same differential you would apply in any other patient (BPPV is common, vestibular migraine is common, Ménière's coexists occasionally).

The Lublin 2014 classification recognises four clinical phenotypes:4 relapsing-remitting MS (RRMS, the commonest at presentation), secondary progressive MS (SPMS, into which most RRMS eventually evolves), primary progressive MS (PPMS, with progressive disability from onset, typically older men), and the clinically isolated syndrome / radiologically isolated syndrome (CIS/RIS, the earliest detectable forms).

Vestibular MS deserves attention as a distinct presentation pattern because the diagnosis is often substantially delayed. A young patient presenting with acute vertigo lasting days — the classic acute vestibular syndrome — is often initially labelled vestibular neuritis, particularly if HINTS is applied carelessly. The clinical clues that should redirect toward central disease in this population: incomplete HINTS pattern (e.g. abnormal head impulse but with central nystagmus features), gait beyond what neuritis would explain, associated visual symptoms (optic neuritis preceding or accompanying), and atypical recovery. MRI with gadolinium contrast is the rate-limiting investigation — order it liberally in the young dizzy patient with any central features.6

Three brainstem regions are particularly important for vestibular MS. The medial longitudinal fasciculus — covered in detail in the next section — produces INO when demyelinated. The vestibular nuclei in the dorsolateral medulla produce central vestibular syndromes when involved, often with hemiataxia or sensory findings. The cerebellar peduncles — particularly the inferior cerebellar peduncle — produce ataxia and downbeat nystagmus when demyelinated. Plaques in any of these regions are commonly silent until specifically tested for, and benefit from a structured oculomotor examination (smooth pursuit, saccades, optokinetic response, head impulse, nystagmus, alignment) in every follow-up.

When you look to one side, both eyes have to move together — one outward, one inward. The brain coordinates this using a narrow bundle of nerve fibres connecting the two sides of the brainstem (the medial longitudinal fasciculus, or MLF). In MS, a patch of demyelination here breaks the coordination: the outward-moving eye works fine, but the inward-moving eye lags or fails to cross the midline. The patient often notices double vision when looking to one side, or describes "blurred vision".

The classic test that confirms this is brainstem-based rather than caused by a weak eye muscle: ask the patient to focus on a target moved close to their nose. The same eye that failed during lateral gaze now moves inward normally. This is preserved convergence — the diagnostic fingerprint of internuclear ophthalmoplegia.

INO results from a lesion of the medial longitudinal fasciculus, the heavily myelinated tract running through the dorsomedial brainstem tegmentum from the abducens nucleus (pons) to the contralateral oculomotor nucleus (midbrain). The MLF carries the signal that yokes the ipsilateral lateral rectus (abduction) to the contralateral medial rectus (adduction) during conjugate horizontal gaze.5

Clinical features of unilateral INO:

• Failure of adduction of the eye on the side of the lesion when looking toward the contralateral side.
• Abducting nystagmus in the contralateral eye on the same lateral gaze attempt.
• Preserved convergence — when the patient focuses on a near target, both eyes adduct normally. The medial rectus subnucleus is intact; the defect is in the connecting pathway, not the effector muscle.
• Skew deviation (vertical misalignment) is present in a substantial minority.
• Vertical pursuit and vestibular eye movements are often abnormal — looking for these adds diagnostic value.

The aetiological split by age is consistent across studies: in patients under 45, MS accounts for the majority of INO cases (often bilateral); in older patients, ischaemic stroke (typically unilateral) is the dominant cause.7 Bilateral INO in a young patient is almost pathognomonic for MS — particularly when accompanied by exotropia in primary gaze (the WEBINOsyndrome, "wall-eyed bilateral INO").

The bedside discrimination of INO has several refinements worth practising. Subtle INO is detected most reliably with rapid horizontal saccades rather than smooth pursuit — ask the patient to switch fixation rapidly between two widely separated targets (your two index fingers, or the tip of your nose and a distant point) and watch for slowness or fatigue of the adducting eye. Quantitative infrared oculography can detect adduction lag of just a few milliseconds — useful in clinical trials and in tracking longitudinal disease activity.6

Differential diagnosis of INO is dominated by two conditions and a handful of mimics. Demyelinating disease (MS) in young patients, often bilateral. Brainstem stroke (particularly small pontine lacunes) in older patients, typically unilateral. Less common but worth considering: Arnold-Chiari malformation, Wernicke encephalopathy, brainstem tumour (glioma, metastasis), Lyme disease, neurosyphilis, Whipple disease, and drug toxicity (tricyclics, opioids, phenothiazines). A myasthenic pseudo-INO can mimic demyelinating INO and improves with edrophonium or rest — worth screening with acetylcholine-receptor antibodies in the right clinical context.5

The functional consequences of INO vary. Some patients report only intermittent diplopia or vague visual blurring; others have disabling oscillopsia when reading or driving. Treatment of the underlying MS with high-dose corticosteroids in acute exacerbations often produces substantial improvement; chronic INO can be managed symptomatically with Fresnel prisms or, where necessary, strabismus surgery. The persistence or recovery of an INO is a useful clinical marker of disease activity that can be followed across visits.

Beyond internuclear ophthalmoplegia, MS can cause several other patterns of dizziness and abnormal eye movements, depending on which part of the brainstem or cerebellum is affected. Most of these are central — meaning the problem is in the brain rather than the inner ear — and can usually be distinguished from inner-ear causes by careful bedside examination and MRI.

Beyond INO, the vestibular and oculomotor features of MS cluster in three main groups:

• Central vestibular syndromes: acute or subacute central vertigo from plaques in or around the vestibular nuclei. The HINTS examination typically shows one or more central features (normal head impulse, direction-changing or vertical nystagmus, skew). MRI with gadolinium shows the enhancing plaque, often in the dorsolateral medulla or middle cerebellar peduncle.
• Central nystagmus patterns: downbeat nystagmus (from cervicomedullary or vestibulocerebellar plaques), pendular nystagmus (characteristic of MS, often asymmetric between the eyes, may improve with memantine or gabapentin), periodic alternating nystagmus, and gaze-evoked nystagmus.
• Cerebellar findings: truncal ataxia, limb ataxia, scanning dysarthria, saccadic dysmetria — the classic Charcot triad of nystagmus, intention tremor, and scanning speech describes late-stage cerebellar MS.

Optic neuritis is the most common cranial-nerve manifestation of MS and may precede or accompany vestibular symptoms. Recognising optic neuritis in a dizzy patient is an important diagnostic clue — and the McDonald 2024 criteria now formally include the optic nerve as a fifth topographic site for dissemination in space, reflecting its central role in early MS diagnosis.3

Two oculomotor features deserve specific clinician-level attention beyond INO. Pendular nystagmus is a distinctive MS-associated nystagmus — typically a small-amplitude, sinusoidal oscillation that is often asymmetric or even monocular, sometimes with vertical and horizontal components dissociated between the eyes. It localises to brainstem-cerebellar circuits and can respond to gabapentin or memantine. Its presence is strongly suggestive of MS in the appropriate clinical context.6

Saccadic dysmetria and saccadic pursuit are subtle but highly localising. Hypermetric saccades (overshoot followed by corrective saccade) point to cerebellar involvement. Saccadic intrusion into smooth pursuit — a pursuit movement broken up by small saccades — is one of the earliest detectable oculomotor signs of MS and is captured well by quantitative eye-tracking.6

Vestibular MS deserves a separate consideration for rehabilitation. Patients with persistent central vestibular deficits — particularly cerebellar — often respond poorly to standard peripheral-vestibular rehabilitation. A targeted programme emphasising gaze stabilisation, balance training in progressively challenging contexts, and habituation to motion-provoking stimuli is more effective. Coordination between the MS neurologist and a vestibular physiotherapist with experience in central vestibular disorders is the practical optimum.

The diagnosis of MS combines the pattern of clinical episodes, MRI evidence of multiple lesions in characteristic locations, and sometimes a spinal-fluid test (lumbar puncture) showing immune-system activity in the brain. The current rule (the "McDonald criteria", most recently updated in 2024) allows a diagnosis to be made earlier than previously possible, because effective treatment started early protects the brain.

Treatment has three parts: treating acute flare-ups (usually with a short course of high-dose steroids), preventing future flare-ups with disease-modifying medicines, and managing symptoms — including specific management of vertigo, double vision, and balance difficulties.

The McDonald criteria, originally published in 2001 and most recently revised in 2024, are the operational framework for MS diagnosis. The core principle is demonstrating dissemination in space (lesions in multiple CNS locations) and dissemination in time (lesions developing or symptoms occurring at multiple time points). The 2017 revisions allowed CSF oligoclonal bands to substitute for dissemination in time.2

The 2024 revisions — published in Lancet Neurology in September 2025 — introduce several important updates:3

• Optic nerve added as a fifth topographic site for dissemination in space (alongside periventricular, cortical/juxtacortical, infratentorial, and spinal locations).
• Dissemination in time may be waived in patients fulfilling dissemination in space when additional biomarkers (CSF kappa free light chains, the central vein sign, or paramagnetic rim lesions) are present — enabling earlier diagnosis from a single MRI in many cases.
• Radiologically isolated syndrome (incidental MS-like lesions on MRI in asymptomatic patients) can now be formally diagnosed as MS under specific criteria.
• Stricter thresholds for patients over 50 and those with vascular risk factors, mitigating the risk of misdiagnosis from age-related white-matter changes.

Management has three components. Acute relapse is treated with high-dose intravenous methylprednisolone (typically 1g daily for 3–5 days); plasma exchange is reserved for severe steroid-refractory attacks. Disease-modifying therapy is stratified by disease activity and patient preference, ranging from injectable platform agents (interferon-β, glatiramer) through oral agents (teriflunomide, dimethyl fumarate, fingolimod, siponimod, ozanimod) to monoclonal antibody infusions (natalizumab, ocrelizumab, ofatumumab, rituximab, alemtuzumab) — progressively more effective and more immunosuppressive.8 Symptomatic management targets specific deficits including spasticity (baclofen, tizanidine), neuropathic pain (gabapentin, pregabalin), fatigue (modafinil, amantadine), bladder dysfunction, and the vestibular and oculomotor symptoms discussed in this module.

Two diagnostic mistakes deserve specific attention. The first is over-diagnosis of MS in patients with non-specific white-matter changes on MRI — particularly older patients with vascular risk factors, in whom small vessel disease produces lesions that meet location criteria but not biological MS criteria. The 2024 revisions explicitly address this with stricter thresholds in older and vascular-risk populations.3 The second is delayed diagnosis in patients presenting predominantly with vestibular symptoms — a young patient with isolated acute vertigo, no other neurological signs, and a normal CT is often discharged with a label of vestibular neuritis. Order MRI with gadolinium liberally in young dizzy patients, particularly when HINTS is incomplete or shows mixed features.

For vestibular-MS symptom management specifically: acute central vertigo from active demyelination responds to high-dose corticosteroids; chronic positional imbalance benefits from vestibular rehabilitation tailored to central deficits; persistent pendular nystagmus may respond to memantine or gabapentin; chronic INO with disabling diplopia can be managed with Fresnel prisms or strabismus surgery in selected cases. The neurology and neuro-ophthalmology services should remain engaged throughout — vestibular medicine in MS is best practised as a multidisciplinary endeavour.

Paediatric MS deserves brief mention as a distinct population: it accounts for approximately 3–5% of MS cases, presents with a higher relapse rate but slower disability accumulation than adult-onset disease, and requires age-appropriate disease-modifying therapy.9