Kleine-Levin Syndrome (KLS)

The Stanford University Center for Narcolepsy has launched a study on Kleine-Levin Syndrome.

• Why this study? answer
• Is Kleine-Levin Syndrome an auto-immune disease? answer
• What is the Stanford project for HLA study in KLS? answer
• Who can enroll? answer
• What do I engage myself to do if I take part? answer
• What is the procedure for enrollment? answer
• What does it cost? answer
• Is there any risk in taking part in the study? answer
• When is the study beginning/ending? answer
• When and how will I receive my results? answer
• Can I change my mind? answer
• Contact information jump

• Why this study?
  Kleine-Levin Syndrome (“KLS”) is a rare sleep disorder characterized by recurrent and unusually long episodes of hypersomnia, associated with behavioral/cognitive disturbances, megaphagia and more rarely sexual disinhibition. These serious episodes alternate with periods without any symptom, normal sleep and behavior typically lasting months to years. KLS primarily strikes adolescents and is self-limiting; cessation of episodes typically occurs in early adult life.

  The cause of KLS is unknown. All diagnostic test results on KLS patients to date, including brain imagery, EEG, serum virus titres, and CSF examination, have been normal. However, nearly half of the patients experience a non-specific, mainly flu-like infectious disease few days before the onset of their first KLS episode. The rarity of the KLS, compared to the high frequency of flu-like diseases in the general population, suggests that some patients may be more predisposed to KLS. This vulnerability may be genetic.

• Is Kleine-Levin Syndrome an auto-immune disease?
  In KLS, the association of an infection before the onset of a disease, a young age at onset, a recurrence of symptoms and possible genetic predisposition is suggestive of an autoimmune disease. Various autoimmune diseases are tightly linked to a specific human leukocyte antigen (HLA) typing (this is a group that is not, like group A, B, O, on our red cells, but on our white cells). The immune system indeed distinguishes self-antigens from foreign antigens through the cell surface expression of the highly polymorphic HLA glycoprotein antigens. HLA system (allele HLA-DQB1*0602) is highly associated with another sleep disorder, narcolepsy. It has been poorly studied in KLS patients, but a recent study in Europe yield a higher than controls frequency of the HLA-DQB1*201 allele in 30 KLS patients, a group that has been associated to various auto-immune diseases. It is now necessary to extend and specify the measure to a much larger number of patients and families.

  Strong evidences for an autoimmune basis in KLS could potentially lead to the testing of drugs or therapy aimed at reducing auto-immunity, which have not been yet, to our knowledge, tested in KLS. This is of particular interest in that severe disease where effective treatment is desperately missing. In addition, the questionnaire will provide the first large survey of the disease and its symptoms. It will also, when compared to questionnaires completed by non-affected healthy subjects, help identify commonalities between patients.

• What is the Stanford project for HLA study in KLS?
  Our group (directed by professor Emmanuel Mignot) in Stanford will measure the HLA group and possible other genetic factors predisposing to KLS in all (115 cases have enrolled) volunteers KLS patients, their parents (80% of parents have agreed to be studied), and compare it to the HLA group in age, sex and ethnic-matched controls (110 cases have enrolled). The study includes questionnaire and blood sampling. The Kleine-Levin Syndrome Foundation (www.klsfoundation.org) funds in part this study and helps its realization. The dates of this project are Jan 2005 until June 2005.

• Who can enroll?
  Any patient who had ever been diagnosed a KLS, whether he/she still suffers from the disease or is now cured. There is no age limit.

  In addition, we would appreciate both parents (one is not sufficient) to give a blood sample too (it helps to better determine the HLA typing). If one parent is unwilling to take part or deceased, do not send anything form the parents, we won’t be able to use it.

• What do I engage myself to do if I take part?
  I will complete a questionnaire (see .pdf or online version) about symptoms of KLS, and have a blood sampling.

  In addition, if possible, I will ask my parents to give a blood sample and answer a quick questionnaire too. Parents and controls can complete the questionnaire either online or by print out and completing a .pdf verson.

• What is the procedure for enrollment?
  <1> First contact Dr. Isabelle Arnulf either by e-mail ( ), phone (650) 724-8839, or fax (650) 725-4913, so that we can explain the detailed procedure and check how it fits with you.

  <2> Read and sign the consent form (.pdf) and the Medical Release Form (.pdf) (to allow us to get all KLS-related records from your primary care giver). It is not mandatory to complete the Medical Release Form in order to participate in this study, but it will help us in our research.

  <3> Complete the KLS questionnaire (.pdf or online version)

  <4> Send all paperwork to Dr. Arnulf, Stanford Center for Narcolepsy, 701B Welch Road, Palo Alto CA 94304 (you can also send the paperwork with your blood sample)

  <5> We will immediately inform you of the receipt, and you will received soon after a blood sampling kit, a procedure for the lab where you will have you blood sample drawn, and pre-paid Fedex return kit

  <6> Have your blood sample drawn in a clinic close to your home. You need to be fasting. You will take these materials (2 tubes with yellow tops and a return box) with you when you have the blood drawn. Most hospitals have blood drawing clinics where you can simply drop in without an appointment to have the blood drawn; we suggest you call beforehand to double check the procedures at whichever facility you choose.

  <7> After the blood is drawn, the tubes go back in the kit, and the kit needs to be put in the nearest Federal Express pickup box as soon as possible. The kit comes with a label instructing Federal Express to bill our account (and not you) and including our address. Tubes will stay at room temperature, no need for dry ice.

• What does it cost?
  We pay for sending and returning the kit via Fedex. The hospital or clinic or doctor's office where you have the blood drawn may charge you for the drawing procedure. Since that research is partly supported by a donation from the Kleine-Levin Foundation, participants may wish to absorb the cost of the blood drawn if not a personal burden to enable further research. If this cost is an issue, you may request reimbursement to process for the reimbursement, we will need a written receipt for the blood-drawing services.

• Is there any risk in taking part in the study?
  The blood drawing may cause bruising or discomfort and in very rare cases, infection and fainting. There is absolutely no risk for the blood drawing to bring on a KLS episode.

• When is the study beginning/ending?
  The study is beginning on January 2005, and will probably end in June 2005.

• When and how will I receive my results?
  We will send to you the results of your HLA typing personally. Since we process a large number of blood samples together, you could have to wait several months before receiving your result. We will also establish a mail list to keep you informed of the general results of the study.

• Can I change my mind?
  Of course. At any time you can withdraw your consent.

CONTACT INFORMATION