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
- 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: email@example.com.
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.
- Physician: You can decide to submit an IDR Form on your patient(s). See “Initiation —
Discussion with Patients,” below.
- 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.
- 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 submitted—so 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 submitted—Month (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 submitted—though 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
9500 Euclid Ave.
Cleveland, OH 44195
FAX: 216 636 3002
Phone: 216 442 5047
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.
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
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
Susac Symptoms Form
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
- Bladder dysfunction
- Apraxia (unable to figure out how to do things that she used to do automatically)
- 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).
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.
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 (firstname.lastname@example.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 (International Disease Registry Form)
CDP Data Collection Forms:
Top Priority Forms:
Lower Priority Forms:
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?
- 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 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.
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**
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.