Clinically Isolated Syndrome | Cedars-Sinai

ABOUT

DIAGNOSIS

TREATMENT

Overview

Clinically isolated syndrome (CIS) is a possible diagnosis for patients who experience an episode that may represent the onset of  multiple sclerosis (MS), a disease of the central nervous system, or may represent an isolated episode that does not require ongoing treatment.

The episode may only affect one area of the central nervous system (monofocal), or multiple areas (multifocal). An experienced medical team, such as the one at Cedars-Sinai Multiple Sclerosis Center, will determine if the episode of symptoms is an indication of multiple sclerosis, and whether the patient is at a high or low risk of developing the disease.

Symptoms

Symptoms of CIS are similar to those of an MS relapse. The main difference between the two conditions is patients with CIS experience only one episode, while MS patients experience multiple episodes.

Symptoms of CIS include:

• Numbness or tingling
• Vision problems, such as double vision
• Spasticity or stiffness of the muscles
• Difficulty controlling the bladder or bowels
• Difficulty with walking and coordination
• Muscle weakness
• Paralysis
• Dizziness
• Shakiness
• Sexual dysfunction

Causes and Risk Factors

Patients with CIS tend to be diagnosed between the ages of 20 and 40, but the condition can occur at any age.

Since the risk of MS is significantly higher when a parent has been diagnosed with the disease, genetic factors may play a role. The unusual relationship between a person’s geographic location during childhood and the risk of MS later in life suggests there may be environmental factors at work in the the risk of CIS or MS.

Diagnosis

Diagnosis of CIS begins with the physician taking a detailed medical history and performing a neurological examination. Because CIS can have similar symptoms of other nervous system disorders, diagnostic tests will help rule out other causes and confirm a diagnosis. These tests may include a magnetic resonance imaging (MRI) scan of the brain and spinal cord.

The patient’s medical team may order a lumbar puncture, also known as a spinal tap, along with cerebrospinal fluid analysis and nerve function tests. Blood tests may be performed to rule out other conditions that have similar symptoms.

Patients diagnosed with CIS will have routine checkups to determine if their condition is progressing toward MS.

Treatment

There is no cure for CIS. The FDA has approved medications to manage the symptoms of certain types of MS and patients diagnosed with high-risk CIS may be prescribed one or more of these to delay the onset of MS and manage symptoms. These medications may be used to reduce the frequency and severity of episodes a patient experiences.

Choosing the right medication requires careful consideration of the risks and benefits, along with close collaboration with an experienced neurologist with experience in treating the disease, such as those at the Cedars-Sinai Department of Neurology.

© 2000-2022 The StayWell Company, LLC. All rights reserved. This information is not intended as a substitute for professional medical care. Always follow your healthcare professional’s instructions.

Clinically Isolated Syndrome (CIS) | National Multiple Sclerosis Society

• Symptoms and Diagnosis of CIS
• Support and Resources for Individuals with CIS

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In this article

What is clinically isolated syndrome (CIS)?

In multiple sclerosis, the immune system attacks the brain, spinal cord and optic nerves. These make up the central nervous system, which controls everything we do. Damage from the attack disrupts signals to and from the brain and causes the symptoms of MS.

Clinically isolated syndrome (CIS) is one of the 4 multiple sclerosis disease courses. CIS refers to a first episode of neurologic symptoms like those in MS. If you experience CIS, you may or may not go on to develop MS.

To be considered CIS, the episode must:

• Last at least 24 hours
• Be caused by inflammation and demyelination (loss of the myelin that covers the nerve cells) in the central nervous system

An episode can include one or more than one symptom. It usually has no associated fever or infection and is followed by a complete or partial recovery.

CIS symptoms

In CIS, your symptoms are linked to where the damage to the myelin occurred in the central nervous system. You may have:

• Vision problems, including optic neuritis, blurred vision, poor contrast or color vision and pain on eye movement
• Numbness or tingling of the face, body or extremities (arms and legs)
• Walking difficulties
• Spasticity
• Fatigue
• Weakness
• Bladder and/or bowel problems
• Dizziness
• Sexual problems

If you are currently experiencing these symptoms, see your healthcare provider. An MS Navigator can help you locate a provider if you don’t already have one.

Who gets CIS, and when?

Like MS, CIS is not directly inherited, and it is not contagious. CIS is 2 to 3 times more common in women than men. Seventy percent of people diagnosed with CIS are between the ages of 20 and 40 years (the average age is 30). But people can develop CIS at older or younger ages.

How is CIS different from MS?

Based upon clinical symptoms alone, CIS and MS may appear the same. In both, damage to the myelin sheath (demyelination) interferes with the way nerve impulses travel to and from the brain, resulting in neurologic symptoms.

• A person with CIS, by definition, is experiencing the first episode of symptoms caused by inflammation and demyelination in the central nervous system. A person with MS has experienced more than one episode.
• With CIS, an MRI may demonstrate damage only in the area responsible for the current symptoms. With MS, there may be multiple lesions on MRI in different areas of the brain and spinal cord.

CIS progression to MS

If you have experienced CIS, you may or may not go on to develop MS. Your healthcare provider will do their best to determine the likelihood of this happening. Here are the criteria they use to make that determination:

• High risk of developing MS: If a provider sees brain lesions similar to those in MS on magnetic resonance imaging (MRI), they predict that you have a 60% to 80% chance of a second neurologic event and diagnosis of MS within several years.
• Low risk of developing MS: If CIS is not accompanied by MRI-detected brain lesions, you have about a 20% chance of developing MS over the same period of time.
• Diagnosis of MS: If CIS is accompanied by MRI findings of old lesions or scars that confirm an earlier episode of damage in a different location in the central nervous system, then an MS diagnosis is confirmed. The presence of oligoclonal bands in a person’s cerebrospinal fluid can also help make the diagnosis.

As MRI technology becomes more advanced, it is likely that the diagnosis of MS will be made more quickly and there will be fewer people diagnosed with CIS. A quicker diagnosis also allows people to get treatment earlier and to slow their disease course.

For those whose CIS does turn into MS, how long does it take?

Not everyone who has an episode of CIS goes on to receive an MS diagnosis. Only 63% of those who experience an episode of CIS go on to receive an MS diagnosis. It is impossible to predict who will and in what period of time. Many factors contribute to this — including some that have not been identified yet.

In addition, many people with CIS are using disease-modifying therapies to delay (and in some cases prevent) MS. If you have had an episode of CIS and are not using a DMT, talk to your healthcare provider about treatment.

What factors influence whether or not CIS turns into MS?

Researchers have recognized multiple variables and risk factors that play a role in the potential for CIS to convert to MS. These include:

• Younger age of disease onset
• Male gender
• The number of MRI lesions
• Oligoclonal bands in cerebrospinal fluid

This list is not exhaustive. (For more details, see a 2021 study about MS biomarkers.) Also, the items in this list do not always apply to each person with CIS. For instance, all men with CIS are not guaranteed to get MS. Finally, there are also a number of risk factors associated with MS, like vitamin D deficiency and smoking, that you can control. If you’d like to learn more about how you can promote your overall health, see the Diet and Nutrition page.

Treatment for clinically isolated syndrome

Treatment with a disease-modifying therapy (DMT) may delay or prevent a second neurologic episode and, therefore, the onset of MS. In addition, early treatment may minimize future disability caused by further inflammation and damage to nerve cells, which can sometimes occur without any noticeable symptoms. If you have CIS, discuss starting a DMT with your healthcare provider if both things are true:

1. You have had one event of MS-like symptoms
2. You have two or more brain lesions on an MRI scan

You and your healthcare provider can take into account your specific risks and benefits and decide whether or not you should start a DMT.

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Cis – Dihydroxydiaminedichloroplatinum (II) (Cis – Dihydroxydiaminedichloroplatinum (II))

Cis-dihydroxydiaminedichloroplatinum belongs to the group of cytological medicines, is not an organic substance. Represents the class of complex ammonium chlorides, bivalent platinum. The drug is widely used in the fight against cancer pathologies of various categories. It has a pronounced mutagenic, cytotoxic, bactericidal effect. The main biological property of cis-dihydroxydiaminedichloroplatinum is the ability to create strong bonds with DNA, leading to the destruction of neoplasms.

Indications for use Cis-dihydroxydiamindichloroplatinum

The drug is used to combat various forms of cancer. The maximum effectiveness of the intake is observed in the following pathologies:

• Germinogenic tumor formations in the ovaries, testicles;
• Oncological processes in the lungs, colon, stomach, esophagus;
• Pathologies in the cervix, uterine body, fallopian tubes;
• Cancer of the ureters, bladder, renal pelvis;
• Osteogenic sarcomas, soft tissue sarcomas, Ewing, uterus;
• Malignant mesithelioma, thymomas, melanomas;
• Oncological formations in the ovaries, prostate, urethra, brain;
• Cervical, penile, skin cancer;
• Lymphomas, neuroblastomas, medulloblastomas, retinoblastomas.

Cis-dihydroxydiamindichloroplatinum: contraindications

The drug is not recommended for patients with impaired auditory function, kidney disease, polyneuritis, depressed hematopoiesis. It is forbidden to treat Cis-dihydroxydiamindichloroplatinum to pregnant women, nursing mothers. When undergoing therapy, patients of childbearing age should use reliable contraception.

Do not take the medication to people with an increased level of sensitivity to its components. Contraindications for taking the medicine:

• Chicken pox;
• Herpes zoster;
• Systemic infectious diseases;
• Gout, nephrolithiasis;
• Previous radiation, chemotherapy based on cytotoxic agents.

Possible side effects of Cis-dihydroxydiamindichloroplatinum

Side effects occur in thirty percent of patients. Among the common reactions of the body:

• Attacks of nausea, vomiting reactions, development of anorexia;
• Stomatitis, leukopenia, thrombocytopenia, anemia;
• Development of amenorrhea, azoospermia;
• Peripheral neuropathies, neuritis;
• Attacks of tachycardia, arterial hypotension;
• Rashes on the skin, swelling, manifestations of nephrotoxicity.

Tel Aviv Medical Clinic Chemical Based Cancer Therapy

Tel Aviv Medical Center develops comprehensive cancer chemotherapy programs. In their work, doctors use advanced diagnostic methods, innovative drugs, unique approaches to creating highly effective treatment programs.

Intraductal breast cancer: symptoms and treatment, cancer in situ (CIS), prognosis

Intraductal breast cancer before 2012 and today – different morphological processes. The current histological classification considers intraductal carcinoma, with the qualifying term “papillary”, not one of the variants of invasive cancer, and even outside of “cancer” according to classical morphological features, but a separate group of papillary lesions, which also includes benign intraductal papilloma.

On the vast majority of Internet sites, the description of the disease is presented in the form of a “hodgepodge” of several malignant processes developing in the milk ducts of the mammary gland, and in no way corresponds to the reality of oncological science.

What is intraductal breast cancer

Intraductal breast cancer, as the name implies, should arise in the epithelium of the lactiferous duct, which has long been questioned by pathologists – specialists who study the cellular structure of tissues. From the latest histological classification of 2012, the very term “ductal cancer” was even removed, stating the occurrence of malignant growth in the structural unit of the mammary gland, which includes both lobules and ducts.

Breast tissue consists of tiny alveoli at the beginning of the lactiferous duct, which is called the “terminal” because of the smallest size among the ducts of the gland. This microscopic community is the terminal lobular ductal structural unit (TLDU), several units form one lobule of the gland, and the ducts of the lobules form the terminal lactiferous duct. Almost fifty such lobules make up a share of the gland with an even larger excretory duct, in total there are one and a half to two dozen lobes in the mammary gland.

Schematically, the structure of the mammary gland can be represented as follows: the entire gland has 15-20 lobes, each lobe has 50 lobules, one lobule has several TDPs. Malignant degeneration does not begin in a separate lobule and not in one duct, but in TDPE.

Ductal carcinoma in situ and intraductal papillary carcinoma are distinct processes, the former originating from the ductal lining epithelium of TDP.

Intraductal papillary carcinoma is certainly a malignant neoplasm, but not in the epithelium, that is, not cancer according to the classical canons. It also appears in TDPE, but on the papillae of a tiny duct, and only in their upper layer, and is essentially a non-invasive neoplasm, that is, it does not penetrate deep into. A small formation occupying only the lumen of the terminal duct does not exclude the vivid clinical manifestations of the disease and even the presence of a nodule in the chest that can be felt by touch.

This morphological variant of the tumor has a somewhat more favorable course than infiltrative breast cancer, although the data on the effectiveness of treatment are based on single scientific reports that have to be revised already from the position of the histological classification changed in 2012, which excluded some forms of malignant processes from circulation and connecting others.

Russian oncological statistics do not give an answer on the incidence of carcinoma, according to various data, the proportion of this cell variant ranges from 0.2% to 4% of all malignant neoplasms of the breast.

Symptoms of intraductal breast cancer

Carcinoma inside the duct practically does not affect women of reproductive age, more than half of the women suffering from this malignant process of the breast fell ill in the postmenopausal period, that is, after 50 years of life.

Clinical manifestations in the mammary gland are diverse, it can be a clearly delimited and displaced node relative to the mammary gland tissues, similar to benign fibroadenoma. Less often, it is possible to develop a tumor that densely merges with the surrounding tissues along the periphery and is motionless relative to the gland.

Most cases of intraductal carcinoma are small and rarely larger than 2 cm. The tumor can be combined with cysts, sometimes the cystic formation exceeds the size of the malignant node. When a papillary formation is located in a large duct of the areola zone, asymmetry of the nipple, its unilateral flattening with fixation, cannot be ruled out.

Metastases in the lymph nodes of the armpit are also possible, but rarely – no more than 2%.

The patient may be disturbed by episodic drawing pain, but this symptom is more characteristic of benign mastopathy. The peculiarity of malignant processes of the mammary gland is precisely in the rarity of the pain syndrome, even with the formation of a skin ulcer. Pain appears when the axillary lymph nodes compress the neurovascular bundle or a significant increase in the mammary gland during cancerous infiltration, when there is no doubt about the nature of the process. For intraductal carcinoma, pain is not typical, but discharge from the nipple is possible. The color of the discharge from the nipple is from transparent to dark brown, the amount is not more than a speck on the linen. It is this symptom that leads a woman to an examination, which makes it possible to identify the disease at an early stage of development.

In any case, the diagnosis cannot be made by eye, a morphological examination of a piece of tissue is necessary.

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Forms of the disease

Until 2012, all intraductal carcinomas were divided into several types according to the cells predominant in their tissue: solid, cribrous, stele flaccid and cystic. According to the appearance of the tumor node, and even more so according to the peculiarities of the course of the disease, due to the small number of observations, scanty differences were found.

The new classification now considers all subspecies to be “equal” malignant types of papillary lesions of the mammary gland, giving each carcinoma a separate column among papillary ones: intraductal, encapsulated and solid. And today, without microscopy, it is impossible to distinguish them by clinical manifestations in the mammary gland, it is believed that the prognosis of encapsulated and solid is more favorable.

For practical oncology, molecular biological characteristics and the degree of aggressiveness of the malignant process of the mammary gland are more important. The disease in question often has a high differentiation and is often positive for hormonal receptors.

Comparing carcinoma with the most common infiltrative cancer, not in favor of the latter, papillary processes are more favorable, which does not negate their purely malignant nature and the possibility of recurrence after surgery, which is due to the spread of malignant cell foci through the system of small ducts. But according to the degree of aggressiveness, papillary forms are two-thirds of high differentiation, that is, low malignancy.

Diagnostic methods

Diagnosis of pathological formations inside the ducts presents certain difficulties, especially with a small nodule. With breast ultrasound and mammography, there are no specific differences between carcinomas and benign papillomas inside the ducts, which occur in every tenth case of breast neoplasms – much more often than malignant papillary carcinomas. In young women of reproductive age, it is benign papilloma that is more common, in older women, breast cancer is more likely.

Ultrasound of the breast is able to visualize a nodular formation, but its connection with the duct is not always obvious, however, with a dense structure of the breast, the resolution of sonography is higher than mammographic examination.

With standard mammography, carcinoma in the duct is not always detected, often its existence is guessed by the expansion of the duct and its deformation. The accumulation of calcium lumps in the tortuous vessels of the tumor testifies to the malignant nature, but calcification is not always present.

Light scanning or diaphanoscopy of the breast in infrared light has no independent significance, the study is harmless to the woman, but for diagnosis it is not enough just to state the fact of pathological changes in the mammary gland. Thermography has the same low information content, showing any pathology of the gland with vague localization. Both methods give colorful pictures of reality, but do not answer the question “what and where”.

Optimal ductography is an x-ray study with injection of a contrast agent into the milk ducts, which allows determining the exact location and size, but not the morphology of the neoplasm.

MRI of the breast is able to detect, localize and describe the formation and even suggest its cellular composition again by the deposition of calcifications in the vasculature.

The simplest analysis is the study of discharge from the nipple under a microscope, cancer cells can be found in the cytological material, but this is a presumptive diagnosis, only a biopsy of the neoplasm will bring clarity. In the presence of a ductal cyst, a puncture is performed, the entire contents of the cavity must be sent for cytology to search for cancer cells.

In order to develop an optimal treatment strategy for breast cancer, it is necessary to determine the cellular composition of the neoplasm before surgery, which is not possible in 100% of cases with an intraductal tumor. The absence of an accurate diagnosis before the operation does not cancel the surgical intervention, morphological diagnostics is performed during the operation, at its very beginning, which excludes the removal of more tissue than the clinical situation requires.

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Possible complications

The most frightening thing for the patient is secretion from the milk ducts, especially dark in color, which is denoted by the term “bleeding mammary gland”. The secret can become infected and cause inflammation with edema and hyperemia of the gland, the formation of a purulent focus.

With a long-term or rapidly growing papillary tumor, blockade of the secretion outflow further along the duct with the formation of a cystic cavity is possible. Infection of the contents of the cyst leads to an abscess with all the ensuing surgical consequences. Opening such a purulent cavity promotes the spread of cancer cells through the blood and lymphatic channels, which subsequently leads to metastases. Against the background of purulent fusion, it is very easy not to notice the cancer focus, sending the “recovered” patient home, so that in a few months she would go to the oncologist with an already widespread carcinoma.

Papillary carcinoma at the beginning of its development is not prone to invasion deep into the tissues, but can develop in other parts of this duct and in other ducts, therefore, insufficient surgical treatment is complicated by early relapse, which, in essence, is a multicentric process not diagnosed in time.

Treatment

Papillary intraductal cancer proceeds favorably, rarely infiltrative relapses in the area of ​​operation and metastases appear later. A small amount of clinical observations of this form of the disease did not allow the development of a separate treatment program, so the choice of tactics is based on the possibility of radical intervention and the tumor’s belonging to a specific molecular biological type: luminal A and B, HER2 positive or triple negative.

Resectable cancer does not guarantee the absence of metastases throughout life, but promises a much longer life. The operations are different, but with this form, preference is given to partial resection of the mammary gland – an organ-preserving intervention. In case of a large tumor of the mammary gland, a mastectomy is performed, and subcutaneous mastectomy is aesthetically better with simultaneous or delayed for several months plastic surgery of the breast defect with a prosthesis.

Metastases in the regional lymph collector, including microscopic ones and those detected during a biopsy of the sentinel lymph node, are surgically removed by removing all the tissue of the axillary, subscapular and subclavian areas along with the lymph nodes located there.

After a partial resection of the mammary gland, postoperative radiation therapy is mandatory, for its start no more than 12 weeks are given, during which it is necessary to carry out preventive chemotherapy, if necessary due to the biological characteristics of the cells. Radiation and chemotherapy are carried out sequentially, their parallel use enhances toxic reactions. After a mastectomy, radiation is required only for metastases in the lymph nodes.

Chemotherapy is preferred before surgery for doubtful operable breast cancer. The low degree of malignancy determines the low effectiveness of preoperative drug exposure. Clinical studies have also shown a lower sensitivity of the primary tumor to a combination of chemotherapy and radiation at the preoperative stage. The choice of tactics is based on the desire of the patient, the molecular type of the neoplasm and the technical possibilities of surgical intervention, since common papillary carcinomas have a very small proportion – hardly 10%.

High cell differentiation leaves much to be desired in the chemotherapy treatment of a generalized and initially widespread process in the mammary gland. The papillary structure is often accompanied by a positive status of sex hormone receptors and allows us to hope for a good effect of endocrine antitumor therapy, both in preventive treatment and when exposed to metastases.

Targeted drugs are indicated when the HER2 receptor is present on tumor cells. Today, the targeted drug is also approved for prophylactic use, including together with hormonal therapy, every 3 weeks for a year, trastuzumab is infused. When the effect of trastuzumab is exhausted, switching to lapatinib is recommended.

In comparison with the most common infiltrative ductal carcinoma, the results of drug treatment of papillary carcinoma are more modest, but the aggressiveness of the course of the processes is also incomparable and not in favor of the infiltrative one.

Prognosis

The survival rate for this variant of carcinoma is high, more than 90% of women live without a breakdown by stages, more than 90% of women live for a decade, 65% survive for a decade, and this is more than the population of those who lived 5 years after treatment of ductal infiltrative cancer.

Detection of the process at an early stage, before the appearance of clinical signs, allows saving more lives; in the form of the malignant process under consideration, it is the early manifestation in the form of secretion that helps to detect an extremely small tumor.

The choice of adequate treatment for papillary breast cancer is a complex problem that has not found a final solution; in each case, the antitumor strategy follows an individual program.

To select the optimal treatment tactics, a strong diagnostic team is needed, armed with the most modern equipment and a laboratory complex. The implementation of the treatment program is not very successful in the absence of clinical experience and broad drug options. In our clinic, we deal with a wide variety of rare types of tumors, and our rich experience cannot but be reflected in the positive results of treatment.

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References:

1. The state of oncological care for the population of Russia in 2018, ed. Kaprina A.D., Starinsky V.V., Petrova G.V./- M.: MNIOI im. P.A. Herzen – branch of the Federal State Budgetary Institution “NMITs Radiology” of the Ministry of Health of Russia; 2019.