What are the other Names for this Condition? (Also known as/Synonyms)

• CIS (Clinically Isolated Syndrome)

What is Clinically Isolated Syndrome? (Definition/Background Information)

• Multiple sclerosis (MS) is a common and chronic autoimmune disorder affecting the central nervous system (brain and spinal cord). In this disorder, the myelin sheath, a protective layer surrounding the nerve cells is progressively destroyed (called demyelination), resulting in associated neurological signs and symptoms
• Clinically Isolated Syndrome (CIS) is described as the first appearance of a single or multiple neurological signs and symptoms lasting 24 hours or more, due to nerve inflammation or demyelination that can be potentially indicative of multiple sclerosis
• Following this episode, most individuals tend to recover fully or partially from the condition, usually within a few weeks. Clinically Isolated Syndrome may remain an “isolated incident” and the recurrence of neurological symptoms may not be observed. However, it is important to note that some individuals experiencing CIS may go on to develop multiple sclerosis
• With Clinically Isolated Syndrome, the healthcare provider has an opportunity to conduct further exams (including MRI scans of the head) and accurately diagnose individuals who may have a higher risk for developing multiple sclerosis. This helps in instituting early treatment measures, termed disease-modifying therapies, that can possibly delay the next episode of symptoms and consequently multiple sclerosis

Who gets Clinically Isolated Syndrome? (Age and Sex Distribution)

• Individuals of any age may develop Clinically Isolated Syndrome, although CIS is commonly observed in young adults, in the 20-40 years’ age group (nearly 70% of the cases are observed in this age group)
• Both males and females are affected, though the condition affects more females than males (2:1 to 3:1 female-male ratio)
• The condition is observed worldwide, and individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Clinically Isolated Syndrome? (Predisposing Factors)

The primary risk factors associated with Clinically Isolated Syndrome include:

• Young adult women are known to have a higher risk
• Family history of multiple sclerosis

The following risk factors are reported for multiple sclerosis (MS):

• Environmental triggers: People living in certain countries with temperate climate, such as Southern Canada, Northern United States, New Zealand, and Europe, report a greater number of MS cases; hence, certain environmental factors may be involved
• People of Northern European descent
• Presence of autoimmune diseases such as type 1 diabetes mellitus and thyroid disease
• Smoking
• Studies have also shown that a lack of vitamin D may lead to MS
• Epstein-Barr virus (EBV) infection
• Individuals with certain HLA gene types have an increased risk for MS

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Clinically Isolated Syndrome? (Etiology)

The exact cause of development of Clinically Isolated Syndrome is unknown.

• However, the neurological symptoms associated with CIS occur when nerve damage results following the inflammation and destruction of myelin sheath, which is the protective layer surrounding the nerve cells. This affects the nerve signals carried to the brain
• The nerve damage may take place at any location in the central nervous system. The demyelination causes the formation of lesions at the location (brain or spinal cord) that may be diagnosed through an MRI radiological scan. CIS may be an early and first indication of a “future” multiple sclerosis
• Multiple sclerosis, which may develop following CIS, is reportedly an autoimmune disorder, wherein the body’s own immune system attacks the nerve cells. The reason behind this is presently unknown but is believed to be associated with certain genetic and environmental factors

What are the Signs and Symptoms of Clinically Isolated Syndrome?

Clinically Isolated Syndrome is classified into two categories based on the episode type and appearance of symptoms:

• Monofocal episode:
  • A specific single area of the central nervous system (CNS) is affected
  • It is typically caused by a single lesion at the affected region and is characterized by a single neurologic sign/symptom
• Multifocal episode:
  • Multiple locations on the CNS may be affected
  • More than one lesions are formed at the affected regions resulting in a set of signs and symptoms

By definition, CIS is the first episode of CNS-related signs and symptoms that lasts for a minimum period of 24 hours. However, the presentation of symptoms is similar to those of multiple sclerosis, and they may include:

Movement-related signs and symptoms:

• Muscle stiffness or spasticity; muscle spasms
• Exaggerated reflexes or hyperreflexia
• Loss of balance
• Coordination difficulties
• Numbness or abnormal sensations
• Difficulties while walking, moving one’s arm or leg; weakness in the arm or leg
• Tremors

Bowel and bladder associated signs and symptoms:

• Constipation
• Difficulty beginning to urinate
• Increased urinary frequency; urgency due to defect in bladder muscle (detrusor muscle)

Visual-related signs and symptoms:

• Double vision
• Eye discomfort
• Loss of vision (one eye at a time may be affected)
• Episodes of optic neuritis: Pain and temporary loss of vision

Other signs and symptoms:

• Decreased attention span
• Depression
• Dizziness
• Hearing loss
• Sexual-related problems
• Fatigue
• Fever or infection is typically absent

The signs and symptoms of Clinically Isolated Syndrome depend on the location of the affected CNS region. It may vary significantly from one individual to another.

How is Clinically Isolated Syndrome Diagnosed?

It is important to diagnose Clinically Isolated Syndrome focusing on the following two factors:

• If the neurological signs and symptoms are the result of nerve cell damage from demyelination
• And, if further evaluation points to an onset of multiple sclerosis

A diagnosis is generally made after ruling out any other underlying conditions affecting the central nervous system. A physician may employ several diagnostic tools, such as the following, to determine CIS:

• Complete evaluation of medical history and family history, along with a thorough physical exam
• Examination of the brain, spinal cord, and eyes
• Specialized blood tests to look for specific antibodies, as well as blood tests to rule out other disorders or conditions with signs and symptoms similar to multiple sclerosis
• Spinal tap: Cerebrospinal fluid is examined for the presence of oligoclonal bands (these are antibodies present in the spinal fluid of individuals with multiple sclerosis)
• Magnetic resonance imaging (MRI) scan of the brain and spinal cord
• Nerve function test

Risk assessment for developing multiple sclerosis (MS):

• Low risk: Following CIS, an MRI scan does not detect the presence of lesions in the brain or spinal cord. In such cases, there is a 20% risk that the individual will develop MS over a period of time
• High risk: Following CIS, an MRI scan does detect the presence of lesions in the brain or spinal cord, which are generally observed in individuals with MS. In such cases, there is a 60-80% risk that the individual will develop MS, over the same period of time

Note: If there is a second episode of neurologic symptoms, then the healthcare provider may recommend another round of testing to identify individuals who have a higher risk for developing MS.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Clinically Isolated Syndrome?

The complications associated with Clinically Isolated Syndrome may include:

• Severe neurological symptoms, in some cases
• There is a potential for the onset of another neurologic episode
• The individual is vulnerable to developing multiple sclerosis
• Emotional stress and anxiety from fear of MS development
• Side effects from use of medication

How is Clinically Isolated Syndrome Treated?

In some individuals with mild symptoms, Clinically Isolated Syndrome may get better without any treatment. For individuals with pronounced symptoms, symptomatic treatment is provided. However, presently, CIS is an incurable condition. The treatment may involve:

• Oral or intravenous steroids, if necessary
• Physical therapy
• Cholinergic medications can be used to decrease urinary-related signs and symptoms
• Anti-depressants may be used for mood or behavior associated conditions

If the condition is suggestive of multiple sclerosis (developing into the future), certain disease-modifying therapies may be recommended or initiated by the healthcare provider, in order to prevent recurrence of another neurological episode, delay MS onset, or potentially mitigate the severity of MS (in future).

Moreover, MS is an immune disorder and several medications to alter the immune system have been approved. The following medications may be administered towards delaying multiple sclerosis onset after careful consideration by the healthcare expert:

• Beta interferons
• Immunosuppressive agents
• Glatiramar acetate (immunomodulator drugs)
• Monoclonal antibodies
• Oral sphingosine 1-phosphate (S1P) receptor modulator medication

How can Clinically Isolated Syndrome be Prevented?

Currently, there are no effective preventative methods available for Clinically Isolated Syndrome.

What is the Prognosis of Clinically Isolated Syndrome? (Outcomes/Resolutions)

• The prognosis of Clinically Isolated Syndrome is generally good, since in many individuals a complete recovery is observed, typically within a few weeks
• It is difficult to predict the development of multiple sclerosis into the future. However, individuals with a higher risk for MS may be recommended early treatment to delay the same, or reduce severity of neurological episodes
• Uncertainty about the development of MS in high risk individuals and those taking preventative medications following CIS, can cause long-term mental stress, frustration, and confusion in them. Occasionally, this may lead to anger in some individuals, which can be identified and addressed by healthcare professionals through counseling and/or education regarding potential development of multiple sclerosis

Additional and Relevant Useful Information for Clinically Isolated Syndrome:

Many researchers consider Clinically Isolated Syndrome as a course of multiple sclerosis disorder.