talking about clinically isolated syndrome or cis

TALKING ABOUT CLINICALLY ISOLATED SYNDROME OR CIS

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What is clinically isolated syndrome(CIS)?Clinically isolated syndrome is an initial episode of inflammatory demyelination in the central nervous system, in other words, a singleobserved attack that puts a person at risk to develop multiple sclerosis(MS) in the future. The definition of an attack is the appearance of a new symptom that lasts for more than 24 hours in the absence offever. Generally, magnetic resonance imaging (MRI) shows lesions(plaques) typical of the disease, but sometimes the MRI is normal.

To diagnose CIS, the patient’s symptoms must be typical of an MS attack: optic neuritis, brainstem or cerebellar symptoms or myelitis.The neurologist must also identify the characteristic signs of an attackin the neurological examination. This episode may present a singleneurological problem (monofocal), e.g., optic neuritis caused by inflammation of the optic nerve. There may be more than one neurological problem at a time (multifocal), e.g., optic neuritis andnumbness on the side of the face (lesion in the brainstem).

Oligodendrocyte(myelin-forming cell)

Myelinsheath

Myelinated nerve(normal axon)

Sclerosis(scarring)

Demyelinated nerve(damaged axon)

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Frequency of Symptoms as the First Signs of MS

Numbness in the limbs 30-50%

Fatigue 20%

Problems with balance or walking 18%

Double vision (diplopia) 17%

Loss of vision in one eye 16%

Dizziness 14%

Paralysis of lower limbs 10%

Urinary problems 10%

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MRI results may point to a certain number of myelin lesions locatedin specific areas of the central nervous system (brain, cerebellum,spinal cord and optic nerves). If that is the case and the person has asecond attack or an increase in the number of lesions on the MRIscan more than 30 days after the CIS episode, a definitive diagnosisof MS can be made.

People who receive a diagnosis of CIS may or may not develop MSsubsequently. Studies have shown that when CIS is accompanied bylesions visible on the MRI which are similar to those observed in MS,the risk of having a second episode and being diagnosed with MS ishigher (approximately 80% in 10 years). When CIS is not accompaniedby typical MS lesions, the risk of having the disease is relatively low(approximately 20% in 10 years).

Whether in the case of a single attack (CIS) or subsequent attacks of MS, symptoms differ from one person to another because they depend on where the lesions are located in the central nervous system.In addition, symptoms fluctuate and are shared by a number ofhealth problems, which complicates their diagnosis.


Frequency of Symptoms Reported During Progression of the Illness

Numbness 90%

Weakness in both legs 90%

Fatigue 80%

Urinary problems 80%

Problems with balance 50-80%

Loss of vision in one eye 65%

Weakness of a limb 52%

Sexual difficulties 50% in women

75% in men

Memory problems 50%

Problems with coordination 45%

Double vision (diplopia) 40%

Abnormal sensations 40%

Pain 40%

Lhermitte’s sign 30%

Facial paralysis 15%

Facial pain (painful twitch) 10%

Epilepsy 5%

Hearing loss 4%

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Ref.: Paty DW, Ebers GC, Multiple Sclerosis, Philadelphia: FA Davis, 1997:135-191.


Diagnostic criteria for CIS There is no one specific examination to diagnose CIS. The neurologistmust mainly base his or her diagnosis on the patient’s medical historyand neurological examination. Because we have a better understandingof MRI technology than we used to, new criteria are now used by radiologists to interpret the results of this test. These criteria allowneurologists to more accurately identify people who have a high riskof multiple sclerosis. This is an important test, but not very specific,because sometimes what appears unusual, and looks like CIS on theMRI, may only be a variation of normal. Consequently, this examinationcannot be used alone to diagnose CIS. The neurologist must thereforebe careful and may also rely on other tests such as lumbar punctureor evoked potential.

Diagnostic process

• Medical history: medical questionnaire allowing the neurologistto get a complete history of the current disorder and identify pastneurological manifestations, if any.

• Physical examination: consists in evaluating vision, cranial nerves,muscular strength, muscle tonus, reflexes, coordination, sensoryfunctions, balance and walking capacities.

• Lumbar puncture (also called a spinal tap): is performed in thelower back to obtain a sample of the cerebrospinal fluid whichflows around the brain and spinal cord and to identify an increasein certain proteins and the presence of oligoclonal bands, whichindicate unusual production of antibodies.

• Visual evoked potential: a procedure that allows the neurologistto measure the time it takes for visual information to reach the brain.

• Magnetic Resonance Imaging (MRI): produces images of lesions inthe white matter (myelin) of the brain, cerebellum and spinal cord.

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Diagnostic criteria for multiple sclerosisTo make a final diagnosis of MS, the neurologist must be convincedthat the myelin has been attacked in two different locations (criterionfor dissemination in space) which cannot be explained by other illnesses.Moreover, the neurologist must also demonstrate that these attacksoccurred at two different periods (criterion for dissemination intime). Accordingly, the medical questionnaire is crucial for correctlyidentifying symptoms and for verifying the medical history to see ifthere were any neurological manifestations in the past.

What should you do if you are diagnosed with CIS?Anyone who has been diagnosed with CIS can continue to live a normal, active life, while monitoring for the possible development of new neurological symptoms. If neurological symptoms recur, ornew ones develop, you should consult with your neurologist sincethis may represent another attack.

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Immunomodulator treatments for CIS are as follows:

Beta interferons:

� Avonex™ 30 µg, intramuscular injection, once a week.

� Betaseron™ 250 µg, subcutaneous injection, every two days.

� Rebif™ 22 µg, subcutaneous injection, once a week.

Glatiramer acetate:

� Copaxone™ 20 µg, subcutaneous injection, every day.

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Therapeutic optionsAfter being diagnosed with CIS, you should discuss therapeutic optionswith your neurologist. There is a consensus among neurologists specializing in MS that it is often preferable to treat the illness at theearliest possible stage, especially when the risk of MS is high.

In Quebec, the four injectable treatments used for multiple sclerosismay also be used for CIS. To do this, the neurologist must obtain theresults of an MRI scan showing a number of lesions located in specificareas of the central nervous system. The patient is often encouragedto participate in choosing his or her treatment, in cooperation withthe neurologist.


These treatments have been used for more than a decade and theirsafety and long-term effectiveness have been proven. Like any drug-based treatment, they can have side effects. The most frequentside effects of beta interferons are flu-like symptoms (fever, headaches,migraines, chills and aches and pains). The intensity of the side effectsvaries and most tend to decrease over time (after approximately three months). These drugs can also disrupt certain biochemical data (disorders of the blood, liver and thyroid functions) and aggravatedepressive states. There may also be redness or pain at the injection site.

Glatiramer acetate also causes side effects, including redness and painat injection sites. There is also a slight risk (10%) that the patient mayexperience chest tightness and difficulty breathing immediately afterthe administration of the drug, which lasts approximately 15 minutes(this rarely happens more than once during the course of treatment).However, these side effects are not dangerous and the chest tightness,which is not always present, does not mean heart failure. There isalso a 10% to 15% risk of lipoatrophy (dents under the skin).

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There are ways of reducing the side effects of the different injectable therapies; ask your physician or neurologist about them.


Therapeutic objectivesTaking immunomodulators may delay the occurrence of a second attack and thus postpone the definitive diagnosis of multiple sclerosis.The treatment may also decrease the severity of attacks and thenumber and volume of lesions identified with the MRI.

If another attack does occur, and depending on its type and intensity,you may be prescribed corticosteroids to reduce inflammation. Theyare taken orally or intravenously (in an outpatient clinic or CLSC) totreat attacks which are disabling (e.g., motor attacks or severe opticneuritis) or accompanied by eye pain. They may reduce the length ofan episode, but their effectiveness varies from one person to anotherand can vary between uses for the same person. This type of treatmentmay have side effects and does not reduce the risk of further attacks.


For the contact information of the chapter nearest you,dial 1-800-268-7582 or visit our website at www.mssociety.ca/qc.

Psychological aspects The period following the diagnosis of CIS may be difficult: the persistence of symptoms, medical examinations and waiting for results are time of considerable uncertainty.

It is important to understand what CIS and MS are so you can makeinformed decisions. Asking for information about the disease is thebest way to relieve stress and take back control of your life. Pleasemake sure that the information is scientifically sound. Don’t hesitateto join the MS Society chapter that is closest to you to ask for information or to talk to someone.


Published by: Communications andServices, Multiple Sclerosis Society ofCanada, Quebec Division

Authors: Dr. François Grand’Maison and Nadine Prévost

Revision and proofreading: Dr. Amit Bar-Or, Dr. J. Marc Girard, Dr. François Grand'Maison, Zofia Laubitz,Nadine Prévost and Diane Rivard

Translation: Barbara McClintock

Graphic design: Kaki Design inc.

Printing: Impression BT

ISBN: 2-921910-23-3Multiple Sclerosis Society of Canada,Quebec Division 2009Legal deposit – 3rd quarter 2009Bibliothèque et Archives nationales du QuébecNational Library of Canada

© Multiple Sclerosis Society of Canada,Quebec Division 2009

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Our MissionTo be a leader in finding a cure for

multiple sclerosis and enabling people affected by MS to enhance their quality of life.

This publication was made possible thanks to an unconditional grant from:

TEVA and the design version thereof are registered trademarks of Teva Pharmaceutical Industries Ltd. and are used under licence.

550 Sherbrooke Street West, East Tower, Suite 1010 Montreal, Quebec H3A 1B9Telephone: 514-849-7591 or 1-800-268-7582 (toll-free)

Fax: 514-849-8914 or 1-877-387-7767 (toll-free)[email protected] www.mssociety.ca/qc


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