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Diseases & Conditions

Susac Syndrome

Susac Syndrome is an autoimmune disease that affects the brain, eye (retina) and inner ear.

Brain Eye Inner Ear
Headache (often migraine-like) Visual disturbance; visual field deficit Hearing loss
Short term memory difficulty The patient notes an area within their field of vision in which they "can't see anything." Tinnitus (ringing, or buzzing in ear---often "roaring")
Slow thought processing Patients describe these areas as a "dark spot," "black spot," "pink spot," or a "hole" in their visual field. Vertigo (whirling dizziness)
Confusion The medical term for this phenomenon is scotoma. Loss of balance
Impaired decision-making and judgment Loss of peripheral vision
Other cognitive dysfunction

This section is intended to help patients, families, their friends, and health care professionals to better understand Susac Syndrome. It is designed to answer questions like:

  • How does Susac Syndrome present?
  • What symptoms and other abnormalities can it produce in the eyes, brain and inner ear?
  • What do we know about the cause?
  • How is it diagnosed or misdiagnosed?
  • How does Susac Syndrome behave over time?
  • How is Susac Syndrome treated and optimally followed?
Brief Description

Susac Syndrome is an autoimmune disease that affects the microvasculature (tiniest arteries and capillaries) of the brain, retina and inner ear---resulting in varying degrees of ischemic injury (injury due to decreased blood flow and oxygen) to these tissues. By autoimmune, we mean that a person's own immune system is mistakenly attacking part of that person's own body. For an explanation of the "immune system" and "autoimmune mistake," go to the section entitled "The Immune System, Autoimmune Mistakes, and the Concept of Immunological Self-Correction" at the end of this section.

Download a PDF to read a brief description Susac Syndrome.

Symptoms

Because Susac Syndrome is due to injury to the microvasculature in the brain, retina, and inner ear, it causes the following categories of symptoms:

  • Brain Symptoms – Cognitive dysfunction and other neurologic symptoms
  • Eye Symptoms – Visual disturbance
  • Inner Ear Symptoms – Hearing loss, Vertigo, Tinnitus

Download a PDF to read a detailed list of the "Symptoms" associated with Susac Syndrome.

Cause

The key to understanding Susac Syndrome is to appreciate the concept of "Autoimmune Endotheliopathy."

  • "Endotheliopathy" means that the endothelial cells (EC) are sick.
  • "Autoimmune" means that the endothelial cells are sick because the person's own immune system is mistakenly waging an attack on those cells, thereby injuring them.

Download a PDF to read more on the "Cause."

Eyes

Ophthalmologic Findings of Susac Syndrome

Autoimmune Endotheliopathy In The Retinal Vasculature

Patients with Susac Syndrome typically notice "dark spots" in one or both of their visual fields. This "dark spot" obstructs their vision in that particular portion of their visual field, so that they "can't see anything" in that particular spot. The patient might say, "When I look at your face, I can't see part of it." Some patients describe this as a "black spot," a "pink spot," or a "shadow." Sometimes, instead, patients complain of "flashing lights" appearing somewhere in their visual field.

Download a PDF to read more on the "Ophthalmologic Findings of Susac Syndrome."

Brain

This MRI reveals 5 obvious "holes in the corpus callosum.

Autoimmune Endotheliopathy in The Brain

The same endothelial cell swelling, loss of tight-junctions, "leakage," and partial/complete occlusion that is going on in the tiny blood vessels of the retina (see "Eye" section) can go on in the microvasculature of the brain and explains the brain disturbances and the typical MRI brain abnormalities of Susac Syndrome.

MRI abnormalities in Susac Syndrome include the following:

  • Abnormalities in the Corpus Callosum:
    • "Snowballs"
    • Linear defects ("Spokes")
    • "Holes"

These corpus callosal abnormalities are located in the central portion of the corpus callosum, as opposed to the under-surface of the corpus callosum.

Download a PDF to read more on the "Autoimmune Endotheliopathy In The Brain."

Ears

Autoimmune Endotheliopathy In The Inner Ear: Audiologic Abnormalities of SS

The third component of the Susac Syndrome clinical triad is inner ear involvement---involvement of the cochlea and the vestibular apparatus. Again, it is an autoimmune endotheliopathy in the microvascular of the inner ear that is the problem. This endotheliopathy leads to narrowing of the channel within the tiny blood vessels that feed the cochlea and vestibular apparatus, and the resultant decreased blood flow and decreased delivery of oxygen and nutrients causes ischemic injury to these tissues.

The figure at right shows the anatomy of the inner ear. Because it is the blood supply to the tip of the cochlea that is most vulnerable, and because the tip of the cochlea is responsible for hearing sounds of low frequency, the autoimmune endotheliopathy of Susac Syndrome primarily causes low frequency sensorineural hearing loss. Loss at other frequencies, however, can also occur. The hearing loss of Susac Syndrome can be on one side, both sides, equal, or unequal. It can develop suddenly, or more progressively. It can be so profound as to require cochlear implants.

Download a PDF to read more on "Autoimmune Endotheliopathy in the Inner Ear."

Clinical Course

The clinical course (how the disease behaves over time) and long term outcome of Susac Syndrome differ from patient to patient. Many patients experience an acute or subacute "monophasic encephalopathic course" (figure to right) that lasts 1-2 years and is not followed by any further disease activity.

If the disease during those 1-2 years is relatively mild or is otherwise easily controlled by immunosuppressive medication, the outcome can be very good, i.e. little or no permanent damage sustained. With more severe disease, more prolonged disease, or both, there is potential for permanent, severe irreversible damage, i.e. varying degrees of dementia, visual loss, and deafness.

Download a PDF to read more about the clinical course of Susac Syndrome.

Treatment

Ideally, treatment of Susac Syndrome should be based on:

  • An accurate understanding of the immunopathogenesis (cause) of the disease.
  • An accurate understanding of the natural history and potential outcome of the disease.
  • The results of controlled clinical trials.
  • Individualized consideration of the risks of under-treatment versus the risks of over-treatment.

Unfortunately, our understanding of the immunopathogenesis of Susac Syndrome is quite incomplete. And, to date, our knowledge of the natural history and treatment of Susac Syndrome is based entirely on anecdotal case reports and retrospective analyses of short series of patients. No comprehensive, systematic and prospective study of the clinical features, clinical course, and treatment of Susac Syndrome has been conducted. No controlled studies of treatment have been conducted.

Download a PDF to read more on "Treatment."

Differential Diagnosis

Many different diseases need to be considered before making a definite diagnosis of Susac Syndrome. Conversely, Susac Syndrome is often misdiagnosed, for example, as "atypical multiple sclerosis (MS)," "unusual demyelinating disease," "atypical ADEM (acute disseminated encephalomyelitis)," or "atypical complex migraine." Therefore, to avoid over-diagnosis and misdiagnosis of Susac Syndrome, it is wise to consider the disease categories listed below:

  • Demyelinating Diseases
  • Autoimmune/Rheumatologic diseases
  • Non-Inflammatory Cerebrovascular disease
  • Infectious CNS disease
  • Malignancy
  • Primary CNS lymphoma
  • Metastatic CNS malignancy
  • Paraneoplastic CNS syndromes
  • Migraine syndromes
  • Meniere's disease
  • Psychiatric disease
  • Other Encephalopathy

Download a PDF to read more on "Differential Diagnosis."

Cleveland Clinic has established a Susac Syndrome Program to provide clinical services for patients with Susac’s syndrome. The Susac’s Syndrome Program, which is directed by Robert Rennebohm, MD, has the following components:

The Susac Syndrome Consultation Clinic

The Susac Syndrome Consultation Clinic is designed to comprehensively evaluate patients with definite or suspected Susac syndrome. This clinic is staffed by a collaborative multi-disciplinary team of specialists–the Susac Team–which is comprised of neurologists, ophthalmologists, rheumatologists, ENT specialists, audiologists, neuro-ophthalmologists, neuro-otologists, and neuro-radiologists who have developed special interest in Susac Syndrome.

Patients may be referred from anywhere in the United States, or internationally. Patients come to Cleveland Clinic for at least 3-4 days, during which time they attend a series of scheduled outpatient appointments with appropriate members of the Susac Team. After each member of the Team has completed their evaluation, the Team draws its conclusions and shares its recommendations with the patient and the patient’s home physicians.

The Susac Syndrome MyConsult Program

The MyConsult Program is an online second opinion service available to patients who would like the Susac Syndrome Program to review their medical records (and associated MRIs, fluorescein angiograms, and other studies) and offer an opinion regarding diagnosis and treatment. Steps involved:

  • Register securely on the Cleveland Clinic MyConsult website.
  • Select Susac Syndrome as your diagnosis, and fill out the appropriate questionnaires.
  • Collect and send the required medical records and studies to Cleveland Clinic.
  • Once all of this information about your illness has been received, it will be placed in a binder and presented to Dr. Rennebohm, Head of the Susac Team.
  • Dr. Rennebohm and other appropriate members of the Susac Team will thoroughly review the information in the binder (including the actual MRI and fluorescein angiography images) and render an opinion regarding diagnosis and treatment.
  • Dr. Rennebohm will then be available to work with your home physicians regarding your further care.

An online medical second opinion for Susac Syndrome costs $565. The MyConsult Program is designed for patients who may not want to, or are unable to, come to Cleveland to attend the Susac Syndrome Consultation Clinic.

The Susac Syndrome Website at Cleveland Clinic

A fundamentally important component of the Susac Syndrome Program is the development and maintenance of the website you are currently viewing.

This website was designed to provide comprehensive education about Susac Syndrome – for physicians, patients, families, and anyone else interested in Susac Syndrome. Patients who attend the Susac Syndrome Consultation Clinic or access the MyConsult Program are encouraged to read through this website.

Learn more about this site.

The International Collaborative Study (ICS) of Susac Syndrome

Another key component of the Susac Syndrome Program is the research component. The ICS is designed to learn as much as we can from as many patients as possible. Please see the Clinical Research section of this website.

International Education

The Susac Syndrome Program is committed to increasing awareness of Susac Syndrome among physicians throughout the world. Accordingly, Dr. Rennebohm and other members of our Susac Team are available to present information about Susac Syndrome at medical institutions and medical meetings anywhere in the world.

Clinical Study: The International Collaborative Study (ICS) of Susac Syndrome (SuS)

The Cleveland Clinic's Study of Susac Syndrome

The International Collaborative Study (ICS) of Susac Syndrome (SuS) is designed to empower patients to share valuable information about their experience with SuS–for the sake of advancing our understanding of this disease, including its clinical course, outcome, and optimal treatment. The ICS has been fully approved by the Institutional Review Board (IRB) at Cleveland Clinic (see Complete IRB Protocol below) and is being conducted by the Susac Team at Cleveland Clinic, under the leadership of Robert Rennebohm, MD. Patients from anywhere in the world may participate. We encourage as many patients as possible to participate–at whatever level they wish (minimally, maximally, or anywhere in-between).

The ICS consists of two separate components:

  • International Disease Registry (IDR)
  • Comprehensive Database Project (CDP)

To participate in the IDR, the patient does not need to sign a Patient Consent Form. To participate in the CDP, the patient must sign a Patient Consent Form.

The IDR

Some patients may want to participate only in the IDR, which is an anonymous Registry. By anonymous, we mean that the data collected for the IDR contains no patient identifying information. (Patients are identified only by a code.) Participation in the IDR involves only a one time completion (by a physician) of a short form (the IDR Form) that briefly and anonymously summarizes basic information about a patient’s case of SuS. (See IDR Form below.)

The "basic information" that is collected on the IDR Form and entered into the IDR is limited to the following:

  • Patient's Age (years and months–for example 33 years, 2 months) when they developed their first symptom(s) of SuS.
  • Patient's Age (years and months) when they were diagnosed with SuS.
  • Patient's Gender.
  • Patient's current Country of Residence (and state of residence if patient resides in USA).
  • Patient’s Home country: (The country the patient views as his/her Home country).
  • Ethnicity of the patient’s mother.
  • Ethnicity of patient’s father.
  • Basic characteristics of Patient’s Susac syndrome (Yes or No answers to the following questions):
    • Has the patient experienced Susac involvement of the brain (e.g. cognitive dysfunction, headache, memory loss, confusion)?
    • Has the patient experienced Susac involvement of the eyes/retina (e.g. scotoma, a dark spot in their vision)?
    • Has the patient experienced Susac involvement of the inner ear (hearing loss, tinnitus, or vestibular dysfunction)?
    • Has the patient had MRI abnormalities characteristic of Susac Syndrome?
      • Did this include lesions in the corpus callosum?

No other data are collected for the IDR. Either your physician or Dr. Rennebohm (if he knows your case well) will complete the IDR Form.

Collection of this “basic information” on as many patients as possible will help us to answer the following questions:

  • How many people in the world have SuS?
  • Is SuS more common in certain countries or certain ethnic populations?
  • What features of SuS are most commonly experienced?

Participation in the IDR requires nothing beyond completion and entry of the IDR Form into our Registry (the IDR). Since the IDR Form contains no patient identifying information, it is not necessary for the patient to sign a Patient Consent Form in order for the IDR Form to be submitted to this anonymous Registry. The patient must, however, receive a Patient Information Sheet about the IDR and must be informed that an IDR Form about their case is being submitted to the IDR. The Patient Information Sheet about the IDR may be found below. It explains how a patient’s case of SuS may be submitted to the IDR. A Physician Information Sheet about the IDR is also provided below, in case a patient wants to show it to their physician.

The CDP

Other patients may want to participate more fully in the ICS–i.e. in the Comprehensive Database Project (CDP). Participation in CDP requires written informed Patient Consent–i.e. the patient must sign a Patient Consent Form.

The purpose of the CDP is to learn details and develop statistics about the clinical presentation, clinical course, and long-term outcome of SuS, including responsiveness of SuS to various treatments.

The CDP collects more extensive and detailed information, than does the IDR. It requires more time, effort, and commitment on the part of the patient---depending on how extensively the patient chooses to participate. Patients will be asked to complete several data collection forms, most of which are self-report questionnaires (see list below). The most important of these forms is the Susac Symptoms Form (see below). The patient (or family member) fills out these forms on-line, using the REDCap data collection system. Please see the Document below that explains the REDCap system.

Also, you might want to look at the Example (see below), which demonstrates the value of having a patient serially complete Susac Symptoms Forms throughout their illness.

For purposes of the CDP, Dr. Rennebohm (and/or his research team at Cleveland Clinic) may also request information from the patient’s medical records–such as a CD of the patient’s MRI and fluorescein angiography studies and copies of selected physician notes.

CDP Data Collection Forms

The actual Data Collection Forms for the CDP may be found below.

How Do I Pursue Participation in the CDP:

First: If you would like to participate in the CDP, or if you would like more information about the CDP, the next step is to email Dr. Rennebohm (rennebr@ccf.org) to express your interest in participation and/or to ask any questions you may have.

Second: In the United States, and particularly at the Cleveland Clinic, HIPAA (Health Insurance Portability and Accountability Act) rules and IRB (institutional Review Board) rules are very strict and are taken very seriously. According to those rules, patients who wish to participate in a clinical study (such as our ICS, beyond the IDR) must not only sign the patient Consent Form, but must also have a phone conversation with Dr. Rennebohm (or a member of our Research Team). The purpose of the phone conversation is to give you (the patient) an opportunity to verbally discuss the ICS with Dr. Rennebohm (or a member of our Research Team) and have all of your questions and concerns verbally addressed. After that phone call, you may then sign and send your Consent Form. Wait until we have had the phone call before you send the Consent Form.

A copy of the Patient Consent Form may be found below.

According to HIPAA and Cleveland Clinic IRB rules, Dr. Rennebohm must document that the above phone conversation has taken place and that the patient has signed the Consent Form after receiving a verbal explanation of the study and verbal responses to any questions they had.

Third: So, if you are interested, and when you are ready, please email Dr. Rennebohm to pursue the Consenting Process. In your email, you may state a preferred phone number and time (your time, not Cleveland time) for Dr. Rennebohm (or another member of our Research Team) to call. If you live in a country outside of the USA or Canada, please include the country code and city code.

After you have completed the phone conversation, and we have received your signed Consent Form, then you will be officially enrolled and we can start collecting information from you by emailing appropriate study forms to you, using the REDCap system.

Again, if you sign a Consent Form to participate in the CDP, you may participate to whatever extent you wish (minimally, or to a greater extent), and you may start whenever you are ready. There are no obligations. We hope that most patients will be willing to at least contribute a “Patient’s Story” and to fill out a Susac Symptoms Form and a Disease Damage Score Form to let us know how they are currently doing. Such information will tell us a lot about the clinical course and outcome of Susac syndrome.

Thank you for considering participation in the ICS.

Sincerely,
Rob Rennebohm, MD
Director, Susac Syndrome Consultation Services
Principal Investigator, International Collaborative Study (ICS) of Susac Syndrome

Crile Bldg, Desk A111, Attn: Janica Petty

Cleveland Clinic
9500 Euclid Ave.
Cleveland, OH 44195
USA

FAX: 216 636 3002
Phone: 216 442 5047
Email: rennebr@ccf.org

IDR Form

IDR Form Page 1


IDR Form Page 2

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Patient Information Sheet: IDR

The Susac Syndrome (SuS) International Disease Registry (IDR) at Cleveland Clinic (CC)

Patient Information Sheet

As a person diagnosed with Susac Syndrome, you are invited to participate in the Susac Syndrome (SuS) International Disease Registry (IDR), which is being maintained by Dr. Robert Rennebohm, Director of the Susac Syndrome Consultation Clinic at the Cleveland Clinic in Ohio.

The main purpose of this research Registry (the IDR) are to:

  • Gain a better idea of how many people in the world have Susac syndrome;
  • Find out where most of these patients live (in which countries);
  • See whether Susac syndrome occurs more frequently in certain countries or certain ethnic groups;
  • Determine what symptoms and abnormalties are most commonly experienced by patients with Susac syndrome.

The goal of the IDR is to collect very basic information, without any personal identifiers, on as many patients with Susac Syndrome as possible, worldwide. Participation ¡n the IDR requires minimal time, effort, and commitment on the part of the patient and involved physicians. It involves a one-time completion of a single IDR Form. No patient identifying information is entered into this Registry. It is an anonymous registry.

The “basic information” that will be collected on the IDR Form and will be entered into the IDR Database is limited to the following information:

  • Patient’s Age (years and months—for example 33 years, 2 months) when they developed their first symptom(s) of Susac syndrome.
  • Patient’s Age (years and months) when they were diagnosed with Susac syndrome.
  • Patient’s Gender.
  • Patient’s current Country of Residence.
  • Patient’s Home country: (The country the patient views as his/her Home country).
  • Ethnicity of the patient’s mother.
  • Ethnicity of patient’s father.
  • Basic characteristics of Patient’s Susac syndrome (Yes or No answers to the following questions):
    • Has the patient experienced Susac involvement of the brain (e.g. cognitive dysfunction, headache, memory loss, confusion, etc.)?
    • Has the patient experienced Susac involvement of the eves/retina (e.g. scotoma, a dark spot in their vision, or fluorescein angiography evidence of Susac involvement of the eyes—-BRAO or vessel hyperfiuoresecence/leakage)?
    • Has the patient experienced Susac involvement of the inner ear (hearing loss, tinnitus, or vestibular dysfunction/vertigo)?
    • Has the patient had MRI abnormalities characteristic of Susac Syndrome?
      • Did this include lesions in the cornus callosum?
    • Age (years and months) when patient first developed brain symptom(s), if developed?
    • Age when patient first developed eye involvement, if developed?
    • Age when patient first developed inner ear involvement, if developed?

No other data is collected on the IDR form. Again, the IDR will contain no patient identifying information. It is an anonymous registry. The IDR Form (please see attachment) has been carefully constructed to assure that it contains no patient identifying information.

How Do I Participate in the IDR

Patients are not able to enroll themselves into the IDR, but may be enrolled in the IDR by one of the physicians who has provided either direct care or consultation. This may include Dr. Rennebohm, if he has been consulted or contacted and involved by either a patient or one of the patient’s physicians and has had contact with the patient.

Your data may be entered into the IDR only after reading this Information Sheet, having all questions answered, and verbally agreeing to participate. You may ask your physician to complete the DR form and submit it to Dr. Rennebohm or your physician may approach you about the IDR, provide this Information Sheet and complete the IDR form. Your data will NOT be entered into the IDR without a discussion with your physician or Dr. Rennebohm and reading of the Information Sheet with your verbal agreement to participate in the IDR.

The IDR involves little or no risk. A potential risk is a risk to the confidentiality of data entered. The IDR has several safeguards in place to protect your identity. As previously stated, no identifying information (e.g. no name, address, birth date, or other actual dates) is entered. Each patient entered will be given a code (ID#). The name of the patient associated with a particular ID# will be known only to the physician submitting the data to the IDR.

Your physician will inform you of your code number (ID#). This is important to help avoid duplication of your information in the IDR. If you may have more than one physician or change physicians, knowing your code number and that you have been entered into the IDR will help avoid duplication. If after receiving your anonymous IDR Form, Dr. Rennebohm suspects your information may already be entered into the IDR, he will ask the submitting physician for additional information from your medical record to clarify if your submission is original or a duplication.

Dr. Rennebohm will maintain the IDR in a password protected database at Cleveland Clinic. Submitted IDR data will not be shared, by Dr. Rennebohm or the submitting physician, with any other individuals or institutions.

You will experience no direct benefit from participating in the IDR. However, collection of this information will allow physicians to gain additional knowledge about Susac syndrome.

Participation in the IDR is voluntary.

Participation in the DR may result in your physicians discussing other available research opportunities with you. For example, there is the Comprehensive Database Project (COP) of the International Collaborative Study (ICS) of Susac Syndrome, which is a more comprehensive study involving serial completion of disease assessment forms and other data collection forms. Participation in the Comprehensive Database Project (CDP) will require you to go through the consenting process and sign a Patient Consent Form.

If you have questions about the IDR, you may contact Robert Rennebohm, MD, Director, Susac Syndrome Consultation Clinic, Crile Bldg. Desk Ahi, Attn: Janica Petty, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, USA. FAX 216 636 3002. Phone: 216 442 5047. Email: rennebr@ccf.org.

If you have questions about your rights as a research subject, you may contact the Cleveland Clinical Institutional Review Board (IRB) at 1-800-223-2273 x 42924.

Asking your physician or Dr. Rennebohm to submit your information into the IDR, indicates your agreement to participate in the research.

Physician Information Sheet: IDR

The Susac Syndrome (SuS) International Disease Registry (IDR) at Cleveland Clinic (CC)

A Sub-Project of the International Collaborative Study (ICS) of SuS
Physician Information Sheet and the IDR Submission Procedure

The Cleveland Clinic (CC) has established a Susac Syndrome (SuS) International Disease Registry (IDR), which is being maintained by Dr. Robert Rennebohm, Director of the Susac Syndrome Consultation Clinic at CC. The IDR has been approved by the Cleveland Clinic Institutional Review Board (IRB). A waiver of the requirement to obtain written informed patient consent has been approved by the IRB, with the understanding that patients will be provided with a Patient Information Sheet. The DR is a sub-project of the ICS.

The purpose of the IDR is to gain an understanding of the world-wide prevalence of Susac syndrome (SuS) by examining ethnic and national occurrences and commonly experienced symptoms and clinical features of SuS by geographic location. The goal of the IDR is to collect very basic information, without any personal identifiers, on as many patients with Susac Syndrome as possible, worldwide. Participation in the IDR requires minimal time, effort, and commitment on the part of the patient and involved physicians. It involves a one-time completion of a single IDR Form. Please see the attached IDR Form. No patient identifying information is entered into this Registry. It is an anonymous Registry.

You are invited to submit your patient’s data to the IDR. You will be asked to complete an IDR Form which asks basic information regarding age at symptoms onset, age at diagnosis, gender, patient’s parent’s ethnicity, and systems involvement. Only physicians can submit IDR Forms to the IDR.

This represents minimal risk research–with the main concern being a risk to the confidentiality of the patient’s information. This risk is minimized by collecting and entering only non-identifiable information. This is an anonymous database. You will be aware of your patient’s identity but are asked to create an anonymous code (IDR Code #) for each patient you enter (see below).

Process for submitting an IDR Form to the IDR at CC:

The initiation of submission of an IDR Form may occur in one of three ways.

  1. Physician: You can decide to submit an IDR Form on your patient(s). See “Initiation — Discussion with Patients,” below.
  2. Patient: Your patient(s) may contact you about their desire to have you submit an IDR Form on their behalf.
    • Please make sure the patient has received the IDR Patient Information Sheet.
    • Offer to complete the IDR Form. That is, work with the patient to assure that all of the information requested is accurately entered.
    • The patient does not need to sign a consent form in order for you to do the above.
  3. Dr. Rennebohm: Through his work as Director of Susac Syndrome Consultation Clinic at CC, Dr. Rennebohm receives calls from physicians and patients from around the world. He may contact you to ask you to consider submitting an IDR Form on any patients with Susac syndrome with whom you have been involved. He may also directly enter a patient’s data into the IDR (based on clinical information he has received regarding the patient), after communication with the patient (and provision of a Patient Information Sheet). If he does not have sufficient data to complete the IDR Form, he will ask the patient’s physician to complete the form.
Initiation — Discussion with Patients

Before completing and submitting an IDR Form on a specific patient, the physician must contact the patient (by phone, email, or letter) to discuss the submission of their de-identified data into the International Disease Registry (IDR). At that same time, the physician will provide the patient with an IDR Patient Information Sheet, which explains the Registry. Key points of explanation include:

  • The purpose and nature of the anonymous IDR,
  • The fact that the IDR form will contain no patient identifying information,
  • The fact that a blank IDR Form is provided for the patient to see,
  • Explanation that, since the data on the IDR Form contains no patient identifying information, the patient does not need to provide consent in order for the physician to submit the completed IDR Form—i.e. the physician is allowed to submit the IDR form without the patient’s consent (since the form contains no patient identifying information); but the physician does want to extend the courtesy of notifying the patient that an anonymous IDR Form about the patient will be submitted to the IDR, and the physician wants the patient to have this Patient Information Sheet.
  • Explanation that the physician will send the patient a copy of the IDR form after it has been completed and submittedso that the patient will know exactly what has been submitted, regarding them.

Assigning a Code (IDR Code #). The entered patient will be identified only by a code that you (the patient’s physician) will construct. The process to assign a code is:

  • Country (in which the physician practices—-the name should be spelled out completely).
  • A number that indicates whether this is the first (1), second (2), third (3), (and so on) patient that the physician has enrolled in the IDR.
  • The physician’s initials (the first letter of their first name, followed by the first letter of their last name, in CAPS).
  • The year of the physician’s birth.
  • The date on which the IDR is being submittedMonth (MM)/Day (DD)/Year (YYYY)
  • For example: the IDR Code # for the first patient enrolled by a Canadian physician with the initials of XT, born in 1972, and submitting the firm on October 12, 2015 would be: Canada-1-XT -1972-10/12/2015

When the enrolling physician submits an IDR Form to the IDR, only the enrolling physician knows the patient name associated with the IDR Code # on the submitted IDR Form. When Dr. Rennebohm receives the submitted IDR Form, he will know the name of the physician associated with that Form, but he will not know the patient’s name or any other patient identifying data about that patient.

When Dr. Rennebohm is the enrolling physician for a patient, he will notify that patient’s physicians that he has enrolled that particular patient in the IDR. If one of those physicians has already enrolled that patient, that physician will notify Dr. Rennebohm of this fact. This will help prevent duplication.

Submission of the IDR Form

After you (the physician) have contacted the patient (via phone, email, or letter), provided the patient with the Patient Information Sheet, and discussed the IDR with the patient (via phone, email, or letter), you may then proceed to complete and submit the IDR Form (mail, fax, or scan-and-email the Form to Dr. Rennebohm). You should provide the patient with a copy of what you have submitted to assure the patient that no identifying information has been submittedthough this is not an IRB requirement.

The enrolling physician may mail, fax, or scan-and-email the completed IDR Form to Dr. Rennebohm, whose contact information is:

Rob Rennebohm, MD
Director, Susac Syndrome Consultation Services
Crile Bldg, Desk Alu, Attn: Janica Petty
Cleveland Clinic
9500 Euclid Ave.
Cleveland, OH 44195
USA

FAX: 216 636 3002
Phone: 216 442 5047
Email: rennebr@ccf.org

To prevent duplicate submissions of the same patient, we have established the following rules:

  • Whenever a physician submits an IDR form on a given patient, the physician must not only notify that patient that an IDR form has been submitted, but the physician must also notify the patient of the patient’s IDR Code #. The patient will be instructed to keep their IDR Code # on file, for potential future reference. The physician will document in the patient’s chart the date on which the physician submitted the IDR form.
  • Before a physician submits an IDR form on a given patient, the physician will ask that patient whether an IDR form about them has ever been submitted by any other physician.
  • As stated above, the patient will know whether an IDR form has ever been submitted about them, because, if so, the patient will have been notified of their IDR code #. Or, if they have forgotten or lost their IDR Code #, they will at least remember that an IDR form was once submitted about them.
  • For example, before Dr. Rennebohm submits an IDR form on a given patient, he will first ask that patient whether an IDR form about them has ever been submitted by any other physician. If not, Dr. Rennebohm will submit an IDR form, notify the patient of their IDR Code #, and will notify the patient’s home physicians that he has submitted an IDR form on their patient. The patient will help Dr. Rennebohm identify the physicians who should be notified. Dr. Rennebohm will use the same coding scheme as will other physicians.
  • What if a patient relocates, comes under the care of new physicians, and one or more of those physicians considers submitting an IDR form on that patient? This Physician Information Sheet instructs the physician to ask that patient, first, whether an IDR form about them has ever been submitted by any other physician. If so, the new physician will know not to submit an IDR form.
  • Please understand that when a physician completes an IDR form on a given patient, the physician either faxes, mails, or scan-and-emails the form to Dr. Rennebohm. Dr. Rennebohm then enters that IDR form into the secure ICS REDCap database (which stores data for both the IDR project and the Comprehensive Database Project), where it is filed under a number that indicates whether it is the first patient consecutively entered into the ICS, or the 1000th, or somewhere in-between. This number is the patient’s ICS #.
  • The actual IDR form entered into the REDCap database will contain no patient identifying information. It will contain the patient’s IDR Code #.
  • In a separate secure file, Dr. Rennebohm will maintain a running list of IDR forms that have been submitted to the IDR. This list will include the ICS #, the IDR Code #, and the physician who submitted the form.
  • If there is any suspicion that two submitted patients (with two different IDR Code #s) might be the same patient, Dr. Rennebohm will be able to contact each submitting physician to determine whether the two patients are, indeed, the same.
  • If two different submitting physicians have the same initials, the same year of birth, and are submitting from the same country, the date of submission will distinguish/differentiate the entered patients.
Future Research

In addition to participation in the IDR, please be aware that there are other research opportunities available to patients with Susac syndrome. For example, patients may want to participate in other projects of the International Collaborative Study (ICS), such as the Comprehensive Database Project (CDP). More information about the ICS may be found in the “Clinical Studies” section of our website (see Link, below). Although participation in the IDR does not require the patient to sign a Patient Consent Form, participation in other projects of the ICS, such as the CDP, does require the patient to sign a Patient Consent Form.

Website Link: http://my.clevelandclinic.org/health/diseases conditions/susac-syndrome

Rob Rennebohm, MD

REDCap Explanation

What is REDCap and How does it work?

REDCap stands for Research Electronic Data Capture. It is a secure online Database system, designed to collect (“capture”), store, secure, organize, and analyze data provided by patients who complete online questionnaires and data collection forms. The data submitted by patients participating in our International Collaborative (ICS) Study of Susac Syndrome are being securely stored, organized, and analyzed by our Susac-specific REDCap Project.

How does the Susac REDCap Project work?

Each patient who signs a Consent Form to participate in our ICS is assigned a Patient ID # and will have their own personal secure “File” within our Susac REDCap Database. The first “Folder” in their File is a “Secure Confidential Patient Enrollment Folder,” which contains the patient’s name, their assigned Patient ID #, their email address, their MRI reports, and other confidential information. The Principal Investigator of the ICS (Dr. Rennebohm) is the only human who has access to this “Secure Confidential Patient Enrollment Folder.” So he is the only person who knows what Patient ID# belongs to which patient. All of the other Folders in the patient’s File are identified only by the anonymous Patient ID #.

Let’s imagine that you are the 30th person to enroll in the ICS. You will be assigned Patient ID # 30, and your REDCap File will be File # 30. I will be the only human being that will know that File #30 belongs to you. All forms/questionnaires that you fill out and submit will automatically be deposited into appropriate Folders within File # 30 (your personal Susac REDCap File).

When I wish to send you a Susac REDCap form (for example, an IDR Form) I direct the REDCap computer to send an IDR Form to the patient associated with File #30. The REDCap computer knows the email address associated with File # 30 and will send the IDR Form to that email address. You will instantaneously receive an email from REDCap. That email will contain a link to your personal Susac REDCap File. When you click on that link, a blank IDR Form will appear. You then fill out the form and click “Submit.” Your submitted form is then instantaneously deposited into the IDR Folder of your personal Susac REDCap File (File #30). In addition to your IDR Folder, your File will also contain a Folder for all of your submitted Susac Symptoms forms, and another Folder for your Susac HAQ forms, and so on.

You will note that none of the blank forms that REDCap sends to you has an ID # on it, nor do the forms request any other patient identifying information. The Forms do not need to have an ID # on them---because REDCap knows that the submitted form belongs to and needs to be deposited in the File associated with the email address to which the form was sent–File #30 in your case. Only the computer (in addition to me) knows that File #30 belongs to the patient with your email address.

At any time, I (and other members of our Research Team) can click on File #30 to see what forms you have submitted, and we can fully view the data entered on each form. Although all members of our Research Team will be able to open the Folders that contain your forms (none of which contain any patient identifying information), I am the only member of our Research Team who can access your “Secure Confidential Patient Enrollment Folder” and will know that you are Patient ID# 30.

Please be aware that some of the forms offer you the opportunity to upload certain documents (e.g. your Patient Story, Medication Flow Sheet, etc.). When you upload such documents, be sure to delete or otherwise obscure any patient identifying information. You may, however, place your Patient ID# on such documents.

One drawback of the REDCap system is that I can email only one Form at a time. If I want to send several Forms to a given patient, I need to send several individual REDCap emails, each containing only one of the Forms.

Another drawback of the REDCap system is that it is not able to send you a copy of the form you have just submitted---nor can it send you the results of past forms you have submitted. We, therefore, strongly encourage you (for the sake of your own records) to make a copy of your completed form before you click on the submit button. To do this, you should “right click” on the screen and choose “print.” That then brings up another screen which gives you the option to save the file as a pdf on your computer.

We want to be careful to not overwhelm you with lots of forms to fill out. In that regard, we want to emphasize that patients may participate in the ICS at whatever level they wish–from minimal, to maximal, and anywhere in-between. Some patients may want to provide an IDR Form and nothing further–and that is okay. Others may be willing and able to participate according to our ideal plans.

Our ideal plans (for patients who are willing and able) are outlined below:

For Newly (or recently) Diagnosed Patients: Our ideal plan is to send (via REDCap emails) the following series of forms (one at a time, gradually, not all at once) to newly (or recently) diagnosed patients:

  • IDR Form
  • Susac Patient’s Story
  • Susac Symptoms Forms (to be filled out to document their status at the time of diagnosis, at the week 1 mark, at week 2, and so on, up to the present time, then at subsequent times in the future).
  • Other forms may also be sent (e.g. Susac HAQ, Susac HL, Susac Mini-T), to document the clinical features and course of their Susac syndrome.

Our goal is to have as many “new patients” as possible complete forms (most importantly, the Susac Symptoms form) at designated times during the course of their illness (more frequently during the first 6 months after diagnosis, then less frequently, eventually 1-2 times per year)–so that we can document the clinical course and outcome of patients, including their responsiveness to the treatment received. Please see the Supplement in the Clinical Study section of our website to see how helpful a patient’s Serial Symptoms Scores can be–both to the patient (and their physicians) and for research purposes.

For “Veteran” Patients (those who were diagnosed more than a year ago–e.g. 5 years ago): Our ideal plan is to gradually (not all at once) send out the following forms:

  • IDR Form
  • Susac Patient’s Story.
  • Susac Symptoms Form (to document current symptoms–e.g. at the 5 year mark).
  • Susac HAQ (to document their current functional capacity and employment status).
  • Susac DDS (to document how much disease damage they think they have sustained).
  • Susac QOL (to document their current Quality of Life–at the 5 year mark, e.g.).
  • Susac VFQ (to document their current vision status).
  • Susac HL, Susac Mini-T, and Susac TSAS (to document their current hearing status).
  • Susac Current Medications (to document whether they are still on any immunosuppressive medications; and, if so, which ones.).
  • Susac Cumulative Medications (to document what immunosuppressive medications they have ever been treated with).
  • Susac Cumulative Manifestations List (to document what specific features and complications of Susac syndrome they have experienced–at any time along the way).
  • Susac SAGE Test (to document their current cognitive ability).
  • They will also be sent a Susac Symptoms form and a Susac HAQ form to complete retrospectively to indicate how they were doing at two early points in time–
    at the time of diagnosis and at the time when their Susac syndrome was a peak severity. (These two times may or may not be the same).
  • The above information will be placed alongside the patient’s MRI and fluorescein angiography (FA) images.

The above data will help us to document and study the clinical course (how the illness behaves over time) and long term outcome of Susac syndrome, including whether patients who are treated in one way do better (or worse) than patients treated in other ways. We will also be able to study whether certain initial MRI findings (or other initial clinical features) require more aggressive initial treatment.

If you have questions, or would like further information about REDCap, please contact Dr. Rennebohm.

Rob Rennebohm, MD
rennebr@ccf.org

Susac Symptoms Form

Susac-Symptoms Hand Form Page 1


Susac-Symptoms Hand Form Page 2

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Susac-Symptoms Hand Form Page 3

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Susac-Symptoms Hand Form Page 4

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Susac-Symptoms Hand Form Page 5

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Susac-Symptoms Hand Form Page 6

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Susac-Symptoms Hand Form Page 7

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Example: Serial Completion of the Susac Symptoms Form

Examples Regarding the Use and Value of the Disease Assessment Forms

To exemplify use of some of the most important Forms of the ICS, and to demonstrate the value of using them, we are sharing Forms that were completed by an actual patient. To preserve the anonymity and privacy of the patient, we have eliminated all patient-identifying information, and we have changed the dates. The patient/family has gladly given us permission to use the patient’s history and their completed Forms for demonstration and teaching purposes. Again, the dates in the history have been purposefully changed.

First, a Summary of the Patient’s Story:

The patient was well until 12/16/13 when she developed numbness and tingling near her mouth and lips and in her hands/fingers. She had also become tired, and was beginning to forget things, often “failing to follow-up on things.”

The above symptoms continued. Then, on 12/30/13 she developed more dramatic and obvious behavioral abnormalities. She became inappropriately giddy and giggly. She seemed unaware of how abnormal she was behaving. Soon she became somewhat incoherent. These symptoms prompted a 911 call and admission to the hospital on 12/31/13. On admission, the following symptoms were evident:

  • Headaches, with vomiting
  • Decreased mental alertness, slow thought processing
  • Short term memory problems
  • Confusion, disorientation, odd behaviors, compromised insight regarding her condition
  • Decreased executive function (disorganized, not able to take care of her affairs or make good decisions)
  • Personality change
  • Emotional lability (giddiness, inappropriate giggling)
  • Marked inability, intellectually, to do her usual work
  • Numbness and tingling (paresthesias)
  • Difficulty walking
  • Imbalance
  • Bladder dysfunction
  • Apraxia (unable to figure out how to do things that she used to do automatically)
  • Vertigo
  • She had no hearing loss or tinnitus (vertigo was her only inner ear symptom)
  • She had no convincing visual symptoms (no scotoma)

On 12/31/13 an MRI revealed several “snowball” lesions in her corpus callosum, as well as several scattered smaller lesions elsewhere in her white matter. (Her MRI looked very much like those shown on this website.) 

Although her diagnosis was unclear at that time, she was treated with 4 consecutive daily pulses of methylprednisolone (1000 mg each), from 1/1/14 through 1/4/14. (See Medication Flow sheet). She improved considerably and rapidly (thanks to the pulses). On 1/5/14 she was discharged, on oral prednisone 60 mg each day.

She continued to improve on a daily basis until 1/10/14 when many of her symptoms again worsened. This prompted re-admission, further evaluation, and further treatment. A fluorescein angiogram (FA) revealed multiple branch retinal artery occlusions (BRAO). A repeat MRI showed new lesions. At this point a definite diagnosis of Susac syndrome was made. Over the next 8 days (1/15-1/22) she received 6 pulses of methylprednisolone, 2 gm/kg IVIG, and was started on Cellcept (mycophenolate mofetil). During this time she improved and stabilized---though a repeat FA study on 1/26 showed new active disease in her retina (since the initial study). On 1/27/14 she was started on rituximab.

Her clinical course since then is depicted by the data on her Susac Symptoms Serial Scores (Example SSS 1-3) and on her Susac Syndrome Medication Flow Sheet (Example MED 1-4). In addition, Example Symptoms A and Example Symptoms B show the actual data entered on the Susac Symptoms form at two different times---time zero (12/31/13) and 17 weeks later (4/29/14).

Comments about the Data on the Forms

Susac Syndrome Medication Flow Sheet:

The Medication Flow Sheet shows exactly what immunosuppressive medications the patient received from onset of treatment through 5/16/14---including the doses and exact dates. The Instructions for use and interpretation of this Flow Sheet may be found in the document entitled “MED Instructions.” Note that this patient has primarily been treated with prednisone, pulses of methylprednisolone, IVIG, Cellcept, and rituximab. Although the option of cyclophosphamide was considered, it was decided to use Cellcept instead. Note that the use of pulses and IVIG was a bit atypical in her case---in that for a period of time she received IVIG once per week, then every 10 days, with an accompanying lower dose of pulse methylprednisolone (250 mg, or 500 mg, rather than 1000 mg).

Susac Symptoms:

Examples A and B show the patient’s actual individual Susac Symptoms scores at time zero (12/31/13, before onset of any treatment) and 17 weeks later (4/29/14). Note that on a scale of 0 to 100---with 0 meaning no symptom and 100 meaning an extremely severe degree of that particular symptom---the patient’s scores for each of the 13 neurologic symptoms were quite high on 12/31/13. For example, her scores for decreased mental alertness, headache, memory impairment, and confusion were 62, 51, 96, and 61, respectively, and the average score for the 13 neurologic symptoms was 69.1. On 4/29/14 those same scores were 4, 0, 2, and 0, respectively, and the average score for the 13 neurologic symptoms was only 1.5---documenting marked improvement.

Note that since the patient was within the first 6 months of her disease, she did not complete the sections regarding Disease Activity and Disease Damage. These two sections, particularly the Disease Damage section, are intended for patients who have experienced their disease for longer than 6 months. Note that by 4/8/14 the patient/family did feel sufficiently comfortable with and capable of commenting on the extent to which they thought any symptoms of unsuppressed active disease were present. They did not think any symptoms of unsuppressed active disease were present---i.e. if there was any active disease still going on at that time, they thought her medications were completely suppressing any symptoms of that active disease.

Susac Symptoms Serial Scores (Susac-SSS):

Note that on 12/31/13 the Total Symptoms Score was 947, the vast majority of it being due to high scores for neurologic symptoms. After her initial treatment with 4 pulses of methylprednisolone (on 1/1-1/4) her total score improved to 500. But, then she worsened (by 1/10), as reflected by her rise in score to 615. After she received more aggressive immunosuppression (1/15-1/27) her score improved to 307, stabilized in that range for a few weeks, then started to further steadily decline towards normal. By 2/26/14 her total score was down to 127, by 3/25 it was 59, by 4/29 it was 19, and by 5/15 it was down to 7.

Note that the measures of Impaired Ability (disability) and impaired Quality of Life (QOL) were also quite severely abnormal on 12/31/13---an average score of 86.7 on a scale of 0-100. By 2/26/14 that score was down to 21.3 and on 5/15/14 it was 6.7---documenting marked improvement in her physical function and QOL.

Also, note her serial QOL scores. On a scale of 0-100, with 100 being the best possible quality of life that is practical to expect, and 0 being the worst quality of life imaginable---the patient’s QOL score was 20 on 12/31/13, quickly improved to 90, and remained in the 90-91 range thereafter.

Concluding Comments:

The main reason for sharing these examples is to demonstrate the value of using these forms---both for research purposes and to facilitate and improve the care of an individual patient.

For an individual patient, the serially collected data allow the patient and their physicians to recognize how well or poorly they are doing. In this patient’s case, there was concern early in her course that she might need cyclophosphamide treatment, if she did not improve with sufficient speed and to sufficient extent. Her serial scores helped the patient and physicians to make the good therapeutic decisions they made—and to document the results of those decisions.

Continued recording of serial scores in this patient’s future will facilitate early recognition of any relapse that might occur at some time in her future (either spontaneously, or due to tapering of medication too much, too soon). If such a relapse does occur, it will be possible to compare its severity to her status during the first weeks of her illness.

So, these forms help the individual patient and physician in the management of that individual case.

But, in addition, imagine how helpful it would be if every new patient were to document the progress of their disease in the same way that the Example patient has. If all new patients were to use these same forms to document the severity and characteristics of their disease at onset and the serial changes that occur after onset of their treatment, we could learn much about the treatment needs, clinical course, and long term outcome of Susac syndrome. We could learn to recognize early indicators of who needs very aggressive immunosuppressive treatment and who might not need as much immunosuppression. We could compare patients to one another. We could document how long Susac syndrome usually remains active, how often Susac syndrome relapses, and when relapse is most likely to occur (or finally stop occurring). We would be able to compare outcomes of patients who started out the same, but were treated in different ways.

Indeed, these forms were designed to not only facilitate and improve individual patient care, but also to uniformly collect data on large numbers of patients for clinical research purposes. The patient/family responsible for these Examples has superbly demonstrated that patients/families can be empowered, enabled, encouraged, and enlisted to serve as thoughtful, competent Patient-Clinical Researchers!!

To see the actual examples, click on the following documents:

Note: It should be realized that some patients whose clinical characteristics at the time of diagnosis are similar to those of our Example patient will not experience the same reassuring course that our Example patient experienced. Some patients with almost the same characteristics at the time of diagnosis will not respond nearly as well, or as fast, as our Example patient did, even when treated in the same way, and sometimes even when treated more aggressively (e.g. with cyclophosphamide). Every patient is different—regarding how much treatment they do or do not need and how quickly they improve; and their treatment needs and clinical course are often very difficult to predict at the time of diagnosis. Some patients, who ultimately do just as well as our Example patient, have a much slower pace of improvement—i.e. it takes a longer time before their Symptoms scores become as low as those of our Example patient.

Data Collection Forms for the CDP

Below are PDF versions of the Data Collection Forms that will be used in the ICS. All of these PDF versions have virtually identical REDCap versions that are imbedded within the REDCap system. The REDCap versions, that patients will be completing on line when they receive their emails from REDCap, are “cleaner,” prettier, and easier to complete and submit on-line, than are the PDF versions. 

For research purposes, patients will complete and submit forms via the REDCap system. For clinical care purposes, patients and physicians are very welcome to use the PDF versions (below) for their own personal use. Most of the PDF versions can be completed on line; some (those with 10 cm visual analog scales) must be printed out and completed by hand.

If a patient/family would like help in understanding how to correctly use any of the forms, they are welcome to contact our Research Team (rennebr@ccf.org)—or, we can connect them with one of several patients who are very familiar with use of these forms (including use of the REDCap system) and are willing to serve as “Mentors for Patient-Researchers.”

IDR Form:

CDP Data Collection Forms:

Top Priority Forms:

Lower Priority Forms:

CPD Sub-Projects

Study of the Spectrum, Clinical Course, Responsiveness to Treatment, and Outcome of Susac Retinal Vasculopathy—A CDP Sub-project:

A major feature of Susac syndrome is retinal vasculopathy (autoimmune microvascular endotheliopathy in the retina). The clinical features of Susac retinal vasculopathy include: scotoma, cotton wool spots, “vessel wall hyperfluorescence”,  “leakage”,  varying degrees of branch retinal artery occlusion (BRAO), capillary dropout, microaneurysms, neovascularization, and vitreous hemorrhage. The nature of this retinal vasculopathy is best revealed by fluorescein angiography (FA). Color retinal photos, OCT and visual field studies also reveal abnormalities.

There is a paucity of information regarding the clinical spectrum of Susac retinal vasculopathy—particularly the natural history, responsiveness to treatment, clinical course, and long-term outcome of Susac retinal vasculopathy. For example, we do not have proven answers to the following questions:

  • When a patient develops a partial or complete BRAO, how much immunosuppressive treatment is needed and for how long? How often is sufficient blood flow restored, and if so, how long does it take to do so?
  • When BRAO develops, does the size of the vessel matter? Is BRAO in a proximal branch retinal artery more threatening than BRAO in tiny vessels out in the far periphery?
  • How soon can immunosuppressive therapy reverse vessel wall hyperfluorescence and leakage? How much long-term immunosuppression is needed to prevent relapse of vessel wall hyperfluorescence, leakage, and BRAO?
  • Is vessel wall hyperfluorescence and leakage always a sign of active immune attack on the vessel? Or, can previously damaged vessels that are no longer experiencing any active immune attack, leak and become hyperfluorescent (simply because of the past damage they sustained)?
  • For how many months or years can an individual patient continue to experience recurrent episodes (clinical or subclinical) of Susac retinal vasculopathy (active immune attack on the microvasculature)? How frequently do such episodes usually occur (how many episodes per year)? Do some patients experience chronic constant continuously active Susac retinal vasculopathy for months/years (as opposed to only intermittently active disease)?
  • What is the long-term outcome of Susac retinal vasculopathy?
    • How severe is the long-term visual impairment—from both the patient’s perspective and the ophthalmologist’s perspective?
    • How many patients develop irreversible damage—e.g. microaneurysms, neovacularization, capillary dropout, vitreous hemorrhage, permanent visual field loss?
    • What do serial OCT studies reveal?
  • What is the role of ultra-wide field fluorescein angiography (Optos) in the evaluation and long-term management of Susac retinal vasculopathy?
  • How is Susac retinal vasculopathy best treated?

To address these questions we will be studying the ophthalmologic evaluations performed on all patients who have agreed to participate in the ICS. This will involve study of FA images sent by patients/physicians.

Long-Term Outcome of Susac Syndrome—A CDP Sub-project:

Little is known about the long term outcome of patients who have had SuS. By “long term outcome” we mean the status of patients 5, 10, 20, 30 years after onset of their disease.

What are patients whose SuS was diagnosed 3, 5, 10, 20, or 30 years ago, now experiencing?

  • How much irreversible damage has the disease caused?
  • How well are patients functioning cognitively?
    • How much memory deficit?
    • How much impairment of “executive function?”
    • How much impairment of thinking ability, thought-processing?
  • How well are they functioning physically?
    • How much difficulty do they have carrying out ordinary Activities of Daily Living (ADL)
    • Have they developed spasticity? To what degree?
    • Have they developed bladder dysfunction? To what degree?
  • What has their “Quality of Life (QOL)” been since experiencing SuS?
  • To what extent did their experience with SuS necessitate vocational changes or adaptations?
  • How are they doing emotionally?
  • What has been the effect of their SuS on their marriage and family life?
  • How much irreversible visual disturbance?
  • How much irreversible hearing loss?

Only limited formal studies of the long-term outcome of SuS have been conducted. The one long-term outcome study that has been published does not include formal neurocognitive or quality of life evaluations (Aubart-Cohen, 2007).

In this Sub-Project, patients will be asked to complete a set of outcome questionnaires to indicate how they are currently doing, and they will be asked to retroactively complete some of those same questionnaires to indicate how they were doing at several different points of time in the past (for example, at the time of diagnosis and at the one year mark). These questionnaires will include:

  • Susac-Symptoms Form
  • Susac-Disease Damage Score (DDS)
  • Susac-HL, Susac-Mini-T, Susac TSAS
  • Susac-Quality of Life (QOL) Questionnaire
  • Susac-HAQ Functional Status Questionnaire
  • Susac-NEI VFQ-25 (Visual Function Questionnaire)
  • Vocational Status Questionnaire
  • Susac-Current Medications
  • Susac-Cumulative Medications

In addition, the following studies will also be obtained to document their current status:

  • Formal visual field, OCT, and FA testing
  • Formal audiometry evaluation
  • Formal, extensive neuro-cognitive testing (if possible), or Susac-SAGE
  • Current or most recent MRI

Clinical Course Graphs:Some willing patients will also be asked to retrospectively draw a free-hand graph of the clinical course of their Susac illness—one graph to depict the level of active disease in the brain over time; one to depict active ophthalmologic involvement, one for hearing loss, and one for tinnitus. These free-hand graphs will be filed in a Compendium of SuS Free Hand Clinical Course Graphs and will be compared to other clinical course data generated by the SuS-ICS. This Compendium will provide many examples of how the SuS of individual patients has behaved over time.

Qualitative research: Some willing patients and families will be interviewed about their experiences with SuS, so that we can hear their voices and document and study what they have to say.

Susac Syndrome and Pregnancy—A CDP Sub-Project:

Several patients with Susac syndrome have first developed their Susac syndrome during a pregnancy. Others have developed their Susac syndrome during the post-partum period. Others have experienced relapses of their Susac syndrome either during a subsequent pregnancy or subsequent post-partum period. As far as we know, all patients with Susac syndrome who have eventually had babies have had perfectly normal babies.

We need more data to determine what percentage of patients with Susac syndrome experience initial disease during either pregnancy or the post-partum period; what percentage of those patients (or other patients) experience relapse during a subsequent pregnancy or post-partum period; how severe are the relapses when they do occur; and what percentage of the babies born in the context of Susac syndrome are perfectly normal?

Data will be collected to better answer these and related questions about Susac syndrome and pregnancy.

Retrospective and Prospective Study of SuS in Children and Adolescents—A CDP Sub-project:

Only a few cases of SuS in children/adolescents have been reported in the international medical literature. It is likely, however, that SuS has been under-diagnosed and under-reported in children, as well as adults. Many pediatricians, including pediatric rheumatologists, ophthalmologists, and neurologists, have either never heard of SuS or are minimally aware of it. Most have never seen a case.

The primary objectives of this sub-study are:

  • To survey the international pediatric rheumatology community, the pediatric ophthalmology community, and the pediatric neurology community (via professional List Serves) to determine how many cases of pediatric SuS have been noted by members of these medical communities.
  • To retrospectively collect and analyze data on the patients so identified, with particular attention to:
    • Clinical characteristics at the time of diagnosis
    • Treatment, including response to various treatments
    • Clinical course: monocyclic, polycyclic, or prolonged continuous?
    • Outcome
  • Comparison of SuS in children vs. SuS in adults
  • To increase physician awareness of SuS in children

Retrospective Study of Treatment of SuS with IVIG, Rituximab, or both—A CDP Sub-project:

The current recommendations for treatment of SuS are based on the treatment of juvenile dermatomyositis (JDM)---a better known and more extensively studied autoimmune microvascular endotheliopathy disorder. The immunosuppressive therapies that have routinely been used for, and have greatly benefitted patients with, JDM have included oral prednisone, pulses of methylprednisolone, IVIG, methotrexate, mycophenolate mofetil, and cyclophosphamide. These same therapies have appeared to greatly benefit patients with SuS.

IVIG:

IVIG is a particularly important treatment option for SuS. It has the best benefit/risk ratio of any therapy used for SuS. Unfortunately, IVIG is very expensive and many insurance companies and governments are unwilling to cover the cost of IVIG treatment—particularly, since there are no formal published studies of a large number of patients that show that IVIG is effective for SuS. It is imperative, therefore, that we collect data regarding the effectiveness of IVIG for SuS.

Rituximab:

The most recently studied new therapy for JDM has been rituximab---an anti-CD20 B cell antibody. Rituximab has been shown to be a promising therapy for a number of autoimmune diseases, including rheumatoid arthritis, lupus, Sjogren’s syndrome, ITP, and autoimmune hemolytic anemia, and multiple sclerosis---as well as juvenile and adult dermatomyositis.

Because rituximab appears to be a promising option for treatment of dermatomyositis, it has been recommended and used as a reasonable innovative option for treatment of SuS (2-4).

Dr. Rennebohm has become aware of at least 15 physicians who have opted to treat SS with rituximab. They and their patients have usually chosen this option because they have viewed it as a less risky alternative to cyclophosphamide and because rituximab has shown potential as a steroid sparing agent. In some instances the rituximab has been added to cyclophosphamide because of the extreme severity/intensity of the disease. Dr. Rennebohm’s subjective impression is that the patients (and their physicians) who have used rituximab believe it has been effective in the majority of, but not all, cases. Since rituximab is increasingly being used for a variety of autoimmune diseases, including dermatomyositis and SuS, it is important to conduct a formal retrospective study to determine the extent to which rituximab has benefited patients with SuS. This would be the first study of rituximab in the treatment of SuS.

To determine whether rituximab is worthy of inclusion in any future clinical trial of treatment for SuS, it is obviously important to retrospectively and systematically study patients with SuS who have already been treated with rituximab.

Bio-Bank Projects—A CDP Sub-project:

In addition to studying clinical aspects of Susac syndrome, an important component of the ICS is the collection of research samples for the analysis of novel biomarkers that may potentially aid in either the diagnosis of Susac syndrome, assessment of disease activity, or understanding of the immunopathogenesis of SS.

The Consent Form will provide an option for blood draws for biomarker analysis, and will seek permission to store any unused cerebral spinal fluid (CSF) from clinical samples for future analysis. Specimens will be collected and processed into either 0.5 ml or 1.0 ml aliquots, boxed, and stored in a minus 70 degree C freezer on site. Funding will be supported by the Fasenmyer Center at Cleveland Clinic.

The potential biomarkers that we are interested in studying include:

  • Circulating endothelial cells (CECs), which is a reliable marker of vascular injury.
  • Endothelial microparticles (MPs), which are potential prognostic markers for endothelial injury.
  • Anti--Endothelial Cell Antibodies (AECA).
  • Soluble fms-like tyrosine kinase-1(sFlt-1), also known as soluble VEGF receptor.
  • Calcitonin gene-related peptide (CGRP).
  • Biomarkers implicated in the pathophysiology of cerebral vasospasm.
  • Exploratory genetic and proteomic studies (with isolation of plasma, DNA, and c-DNA).

The above biomarker and genetic studies will be done in conjunction with already existing studies being conducted by Rheumatology (Drs. Calabrese and Hajj-Ali) and Ophthalmology (Dr. Srivastava) at Cleveland Clinic.

We will also be establishing a brain biopsy bank: Some patients who enroll in the ICS will have had brain biopsies. With the consent of these patients, we will request their biopsy materials for study.

Patient Consent Form for the CDP

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Privacy Protection

The database product that will be used to obtain and store data will be REDCap. All computers used will be encrypted and password protected. The SuS Research Team at the Cleveland Clinic will be responsible for maintaining the computer system and entering and maintaining the data. Sub-investigators will be able to obtain data only through the permission of the Principal Investigator.

All study material will be coded with a participant ID number. The key for the participant ID number and the corresponding participant name will be stored (in the Secure Confidential Patient File) within the computer used for the study. All files will be triple password protected. Back-up disks for the system will be stored in a locked filing cabinet. Following analysis, all data will be stored in disks and given to the Principal Investigator for confidential secured storage.

In the event that patient information in this registry is to be shared (for research purposes) with any colleagues outside of Cleveland Clinic, all patient identifiers will have been removed—such that the only identifier of the data is the code ID number.

IRB Approval for the ICS - The Complete IRB Protocol

The International Collaborative Study (ICS) of Susac Syndrome has been fully approved by the IRB (Institutional Review Board) at Cleveland Clinic (CCF IRB # 13-188).

To view or download the complete IRB proposal.

Inclusion and Exclusion Criteria

Patients may participate in the ICS if they have received a diagnosis of definite, probable, or possible Susac syndrome from their personal physician. Patients will be enrolled if they have experienced at least one component of the Susac triad (encephalopathy, retinal vasculopathy, or inner ear disease), if other plausible explanations for their illness have been deemed less likely by their personal physician and by the Principal Investigator’s review of the patient’s medical records, and if the patient has signed formal written consent.

Cleveland Clinic Release of Medical Records Form

View and download the Authorization for the Release of Medical Information from Other Healthcare Facilities.

In 1975 Dr. Susac saw a young woman with a previously unreported combination of problems – a clinical triad of:

  • Encephalopathy
  • Branch retinal artery occlusions (BRAO)
  • Deafness

Shortly thereafter, Dr. John Selhorst referred to Dr. Susac a 40 year old woman with an identical set of clinical findings. In 1979 Drs. Susac, Selhorst, and John Hardiman (the neuropathologist at the Armed Forces Institute of Pathology who interpreted the brain biopsy in the Selhorst case) published a report of these two cases. The title of the report wasMicroangiopathy of the Brain and Retina.

In 1986, Dr. Susac presented a 26 year-old woman with this syndrome to the Dr. William Hoyt at a Neuro-ophthalmological Symposium held in Dr. Hoyt's honor in San Francisco. When Dr. Hoyt, one of the nation's most eminent neuro-ophthalmologists, saw the branch retinal artery occlusions, he announced the diagnosis as "Susac Syndrome."

Because the syndrome is very commonly misdiagnosed as "atypical multiple sclerosis (MS)," Dr. Robert Daroff, then Editor-in-Chief of the medical journal Neurology, asked Dr. Susac to write a brief article on the syndrome for neurologists (1994). Dr. Daroff insisted that the article be entitled "Susac Syndrome." The disease has been called "Susac Syndrome" ever since.

Since the initial report, approximately 300 patients with Susac Syndrome have been reported in the medical literature.

In 2005, at a Susac Syndrome Symposium organized by Dr. Martin Lubow at Ohio State University, Dr. Rennebohm presented to Dr. Susac a case of an adolescent with Susac Syndrome. At that symposium a concept of emphasis was that Susac Syndrome represents an "autoimmune endotheliopathy" and that the immunopathogenesis and treatment of juvenile dermatomyositis might serve as a helpful model in better understanding, treating, and studying Susac Syndrome.

By 2008 it became obvious to Drs. Susac and Rennebohm that an International Collaborative Study of Susac Syndrome would be the most effective and efficient way to increase knowledge about Susac's Syndrome. Accordingly, Drs. Susac and Rennebohm teamed up to create the content on this website to both facilitate the Susac's Syndrome International Collaborative Study and to serve as a major source of education about Susac Syndrome.

The international Neurology community, and Medicine in general, lost one of its greatest clinicians when Dr. Susac died in February, 2012 at the age of nearly 72. He was still generously and compassionately helping patients with Susac syndrome (and their physicians) until a few weeks before his death.

In July, 2012 Dr. Rennebohm moved from Calgary to the Cleveland Clinic to establish and direct a comprehensive Susac Syndrome Program, which includes an International Susac Syndrome Consultation Service and continuation of the International Collaborative Study of Susac Syndrome.

My Personal Story written by Yvonne Heerema

In January 1993 I was a busy family practitioner in Calgary, Alberta and I thought that things were pretty normal except that I was about 8 weeks pregnant and was getting over a cold that had turned into sinusitis. I had one episode of severe dizziness at the end of January. I was more tired than usual and had some trouble focusing on things, but I blamed all my symptoms on early pregnancy. My family, however, had a more significant awareness of what was occurring, and on February 10, 1993 my sister rushed to my house after a bizarre phone conversation, during which I seemed very confused, and brought me directly to my family doctor`s office.

My doctor was alarmed at my slow and abnormal thought processing and sent me straight to the hospital where I was admitted. In hospital I was found to be quite confused and had lost most of my short term memory. I became dizzy and rapidly lost my coordination when walking. Shortly after admission I developed nausea and vomiting and required an intravenous drip to correct dehydration.

There was a series of lab tests, an electroencephalogram, lumbar puncture and a MRI of my head. The tests showed general slowing of my brain waves while the MRI showed widespread abnormal spots throughout the brain. The spinal fluid had an unusually high protein content, no white blood cells and no sign of infection.

My mental functioning decreased significantly during the first week of hospitalization and I was treated with intravenous steroids for three days (pulse methyl prednisone) followed by oral high dose steroids (Prednisone 8o mg daily). An initial diagnosis of atypical multiple sclerosis was made and I was discharged to be followed up in the multiple sclerosis (MS) clinic. I was too ill to worry or think while in the hospital and just slept. In truth I had a severe sickness of the brain which is called encephalopathy and I had lost the ability for normal thought.

Read the rest of Yvonne's story

This contact information is primarily offered for questions regarding the SuS-International Collaborative Study. We suggest that:

  • Any questions about the diagnosis and treatment of an individual patient be channelled through the patient’s physician.
  • Visitors realize that the material on this website has been designed for information purposes only. It should not be used in place of medical advice, instruction and/or treatment. If you have specific questions, please consult your doctor or appropriate healthcare professional.
Robert Rennebohm, MD
  • Director of the of Susac Syndrome Program at Cleveland Clinic
  • E-mail: rennebr@ccf.org
  • Phone number: 216.445.6626 or 216.444.2400

Susac Syndrome Program Mailing Address

Susac Syndrome Program
Crile Bldg, Desk A111
c/o Margaret LaPlaca
Cleveland Clinic
9500 Euclid Ave.
Cleveland, OH 44195

Online Second Opinion

The MyConsult Program is an online second opinion service available to patients who would like the Susac Syndrome Program to review their medical records (and associated MRIs, fluorescein angiograms, and other studies) and offer an opinion regarding diagnosis and treatment.

Articles on Susac Syndrome