Both multiple sclerosis (MS) and clinically isolated syndrome (CIS) are complex autoimmune neurodegenerative diseases with multiple etiological triggers.

Clinically isolated syndrome (CIS) is usually considered the first episode of multiple sclerosis (MS). However, this does not mean all patients with CIS will develop MS.

• Studies state that about 60 to 85 percent of all patients with MS had clinical symptoms of CIS about 20 years before being diagnosed with MS.
• However, the exact pattern of the shift from CIS to more advanced stages is unclear.

The risk of developing MS increases by 60 to 80 percent when a magnetic resonance imaging (MRI) of a patient with CIS detects brain lesions identical to those found in MS. This patient is likely to develop a second episode of neurological conditions or is diagnosed with MS within a few years.

If an MRI of a CIS patient does not show any brain lesions, the probability of acquiring MS is low (about 20 percent).

Comprehensive cohort studies on the natural history of CIS have demonstrated that people diagnosed with CIS may go through four stages:

1. Clinically isolated syndrome (CIS)
2. Relapsing-remitting multiple sclerosis (RRMS)
3. Secondary progressive multiple sclerosis (SPMS)
4. Death

What is the difference between CIS and MS?

Both multiple sclerosis (MS) and clinically isolated syndrome (CIS) are complex autoimmune neurodegenerative diseases with multiple etiological triggers. The myelin sheath around the neuron is damaged (demyelination). This leads to interference in the transmission of nerve impulses throughout the nervous system, resulting in various neurological conditions.

Clinically isolated syndrome (CIS)

• CIS is a single episode of neurological condition that lasts for up to 24 hours, usually affecting optic nerves, brain stem, or spinal cord.
• A magnetic resonance imaging (MRI) of a person with CIS may indicate damage just in the location, causing the current symptoms.
• The treatment for CIS depends on the symptoms; an acute episode may require intravenous steroid application.

Multiple sclerosis (MS)

• MS is a lifelong condition with multiple flare-ups of various neurological conditions, including vision problems, mobility issues, cognitive impairment, etc.
• The condition is said to be MS only after the occurrence of a secondary clinical episode of CIS.
• An MRI with MS may show several lesions in various parts of the brain and spinal cord.
• The cerebrospinal fluid shows oligoclonal bands.
• Both sensory and motor nerves are tested for their evoked potential to evaluate MS.
• MS is treated with various drugs, including symptomatic treatment, steroids, and disease-modifying drugs, to reduce the occurrence of MS flare-ups.

What are the symptoms of clinically isolated syndrome?

The symptoms of the patient will be determined by the location of the injury in the brain or spinal cord. Patients with the clinically isolated syndrome (CIS) commonly experience the following symptoms:

• Fatigue
• Dizziness
• Vision problems
• Numbness
• Tingling
• Muscle weakness
• Muscle stiffness
• Uncontrolled movements
• Paralysis
• Difficulty walking and coordinating
• Sexual dysfunction
• Bladder and bowel incontinence

4 disorders associated with CIS

1. Optic neuritis: The optic nerve is responsible for sending the stimulus of an image formed on the retina, which is at the back of the eye. Damage, swelling, or inflammation to the optic nerve is called optic neuritis. It can happen instantly or develop gradually over time. Optic neuritis causes pain and temporary vision loss. Blind patches or areas of impaired vision surrounded by an area of normal vision are the common symptoms of optic neuritis. Color vision can be significantly impaired, and the patient may suffer pain, especially while moving the eyes.
2. Transverse myelitis: Transverse myelitis is a condition developed when the spinal cord is damaged. The development of symptoms can be abrupt, lasting one to two hours, or develop gradually, lasting for one to two weeks. The developed symptoms solely depend on the region of the spinal cord that is injured and the affected area of the body. Muscle weakness, numbness, or tingling in the toes, bladder, and bowel incontinence are the most common symptoms.
3. Lhermitte’s sign: Also called barber's chair syndrome, Lhermitte’s sign is a sudden feeling of electric shock that travels down through the neck to the spinal column, radiating down to the fingers and toes.
4. Brainstem syndrome: Damage to the nerves at the base of the brain where it connects to the spinal cord leads to brainstem syndrome. The brainstem regulates basic activities including breathing, heart rhythm, and blood pressure. The symptoms of brainstem syndrome include dizziness or vertigo, nausea, vomiting, and double vision. However, symptoms vary depending on the region involved.

All the disorders are distinct and not everyone who experiences these disorders will develop additional symptoms of multiple sclerosis.

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What are the risk factors of clinically isolated syndrome (CIS)?

Clinically isolated syndrome (CIS) is caused when immune cells attack healthy nerve cells, resulting in demyelination of the nerves.

The risk factors are not clearly understood but studies have revealed the association of CIS with certain factors including:

• Age: Though CIS can be developed at any age, it is mostly seen among individuals aged 20 to 40 years old.
• Hereditary: If a parent is diagnosed with multiple sclerosis (MS), there is a possibility that their child can develop CIS or eventually MS.

What are the treatment options for clinically isolated syndrome?

There is no definitive cure for the clinically isolated syndrome (CIS). Usually, the episodes of CIS are short, lasting for not more than 24 hours. In extreme cases, the symptoms subside within a few weeks. These symptoms usually resolve on their own without the necessity of active management. In some cases, steroids may be administered.

Severe symptoms, such as vision loss and vertigo, are treated symptomatically, and high doses of steroids are administered in the hospital setting. Steroids can accelerate recovery. Nevertheless, whether the patient receives steroids, the overall rate of recovery will be the same.

If the magnetic resonance imaging (MRI) of a patient with CIS indicates a higher chance of acquiring multiple sclerosis (MS), the neurologist may recommend disease-modifying treatment (DMD) recommended by the U.S. Food and Drug Administration (FDA).

Studies report that beginning with disease-modifying medication after CIS slows down the emergence of MS. However, the advantages of disease-modifying medication therapy following CIS remain debatable.

What kind of disease is multiple sclerosis?
See Answer

How is clinically isolated syndrome diagnosed?

A neurologist diagnoses clinically isolated syndrome (CIS). There is no one physical examination or diagnostic test that can be used to diagnose CIS. The procedure involves ruling out other probable reasons for the symptoms. A clinical evaluation and medical history of the patient are crucial.

• Medical history
  • Thorough medical history is necessary to confirm the diagnosis of CIS. To make the diagnosis of the condition as CIS, the patient should never have any neurological symptoms of a prior episode of CIS. If present, then the diagnosis is multiple sclerosis (MS).
• Neurological evaluation
  • A neurologist can perform a variety of easy tests to either propose or rule out a cause for the symptoms. These include testing of mobility, coordination, eyesight, balance, reflexes, and other sensory functions in the patient. The results of these tests can help identify whether the patient has CIS and where the damage has occurred in the central nervous system.
• Blood tests
  • Though there are no definitive blood tests to confirm the diagnosis of CIS or MS, various blood tests are performed to discover or rule out other potential reasons for the symptoms.
• MRI scan
  • The most frequent test is a magnetic resonance imaging (MRI) scan of the brain and spinal cord. An MRI can identify microscopic scars or lesions produced by demyelination, which appear on the scan picture as little white patches. Before performing the scan, gadolinium dye may be injected into a vein to assist the radiologist and neurologist distinguish active regions of inflammation and any older areas of scarring that could be present.
  • The optic nerve, spinal cord, and brainstem are the most often damaged sites in CIS.