Clinically Isolated Syndrome (CIS)

What clinically isolated syndrome means

"Clinically isolated" means there has been one clinical attack. "Syndrome" means a recognizable pattern of symptoms. The attack is caused by the immune system damaging myelin in one area (monofocal CIS) or more than one area at the same time (multifocal CIS).

To count as CIS:

• symptoms last at least 24 hours
• there is no fever or infection that could explain them
• they fit a typical demyelinating pattern
• no other diagnosis explains them better

The 2017 McDonald criteria, and later revisions, allow doctors to diagnose MS at the very first attack if tests show signs of disease spread in both space (different parts of the nervous system) and time (old and new damage). So some people who would once have been told they had CIS now receive an MS diagnosis straight away.

Symptoms by location

Optic neuritis is the first event in about a fifth of people who later develop MS. Symptoms typically build over hours to days, plateau, then slowly improve over weeks.

How CIS is diagnosed

1. Neurological exam: vision and color testing, eye movements, reflexes, sensation, strength and coordination.
2. MRI of the brain and spinal cord with contrast: the key test. It shows the lesion causing symptoms and any silent lesions elsewhere. Lesions in typical MS locations (next to the ventricles, just under the cortex, in the brainstem or spinal cord) matter most. A mix of enhancing (active) and non-enhancing (older) lesions shows dissemination in time.
3. Lumbar puncture: oligoclonal bands in the spinal fluid but not the blood show antibody production inside the nervous system. Under the McDonald criteria, they can substitute for dissemination in time.
4. Blood tests to rule out mimics: aquaporin-4 and MOG antibodies (for neuromyelitis optica spectrum disorder and MOG antibody disease), vitamin B12, thyroid function, and tests for infections or other autoimmune diseases when appropriate.
5. Optical coherence tomography and visual evoked potentials in optic neuritis.

What is the risk of developing MS after CIS?

The MRI at the time of CIS is the strongest predictor.

Other factors that raise the risk:

• oligoclonal bands in the spinal fluid
• lesions in the spinal cord or infratentorial area (brainstem and cerebellum)
• enhancing lesions at the first scan
• younger age at onset
• low vitamin D and smoking

Factors linked to a lower risk include isolated optic neuritis with a normal MRI, and good recovery from the first episode.

Treatment

Treating the attack

Mild symptoms often recover without treatment. For disabling symptoms, such as poor vision or weakness, a short course of high-dose steroids (usually IV methylprednisolone for 3 to 5 days, or high-dose tablets) speeds recovery. Steroids do not change the long-term outcome. Plasma exchange is used for severe attacks that do not respond.

Lowering the risk of MS

For people with CIS and MRI findings that suggest a high risk of MS, starting a disease-modifying therapy (DMT) early delays a second attack and reduces new MRI lesions. In the US, many DMTs, including interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate and the anti-CD20 antibodies, are approved for relapsing forms of MS that include CIS. The choice depends on risk, side effects, pregnancy plans and personal preference.

People with a normal MRI are usually monitored with repeat scans rather than treated.

Monitoring

A repeat MRI at around 6 to 12 months, then periodically, checks for new lesions. A new lesion or a second clinical attack confirms multiple sclerosis.

Outlook

Recovery from the first episode is usually good: most people with optic neuritis regain near-normal vision within months. Some never have another event. For those who do develop MS, starting treatment early is linked to less disability in the long run.

Things you can do: stop smoking, keep vitamin D levels in a healthy range (ask your doctor about testing), stay active, and report any new symptom lasting more than 24 hours.

Frequently asked questions

Is clinically isolated syndrome the same as MS?

Not necessarily. CIS is a first episode of myelin damage. It becomes MS only when there is evidence of disease spread in space and time, either from a second attack or from MRI and spinal fluid findings. Some people with CIS never develop MS.

What are the most common symptoms of CIS?

The most common are blurred or dim vision in one eye with pain on eye movement (optic neuritis), numbness or tingling in the legs or trunk, a tight band around the chest, double vision, vertigo and unsteady walking. Symptoms last at least 24 hours.

How likely is CIS to turn into MS?

It depends mostly on the MRI. If the brain MRI shows other lesions typical of MS, the long-term risk is roughly 60 to 80%. If the MRI is otherwise normal, the risk is about 20%. Spinal fluid oligoclonal bands raise the risk.

Should CIS be treated with MS drugs?

For people with MRI or spinal fluid findings that suggest a high risk of MS, neurologists usually recommend starting a disease-modifying therapy, which delays a second attack. People with a normal MRI are usually monitored instead. The decision is made with a neurologist.

Can stress or an infection trigger CIS?

Infections sometimes come shortly before demyelinating episodes, and Epstein-Barr virus infection earlier in life is strongly linked to MS risk. Stress has a weaker link. If symptoms come with fever or follow a recent infection, doctors also consider acute disseminated encephalomyelitis (ADEM), a different condition (see ADEM).