|
HHUGS In the News HH Research |
|
HH Surgery Kings
College Hospital Montreal Neurological Institute
HH
Media
Archive
|
New HH Study Underway at RCH, Melbourne Following on from their groundbreaking surgical program on HH, the team from the Royal Children's Hospital (RCH) in Melbourne, Australia are currently undertaking a new research study into the causes and effects of hypothalamic hamartoma, which hopefully will answer some of the many questions about why the hamartomas develop, how they cause epilepsy and why they often cause problems with behaviour and learning. The researchers are: The research will centre on those children who have had a HH removed at the RCH or who have been referred for evaluation to the Children's Epilepsy Program. The research will consist of:
According to Dr Freeman, the research team are trying to test the theory that a HH develops because of a "somatic mutation" in the DNA of the brain. "These type of mutations happen after a baby is conceived", says Dr Freeman, " and only affect some cells in the body. If we find a mutation like this, it will not mean that your child got this mutation from you or that they could pass it on to their children. It will just help us to understand how these hamartomas develop". Dr Freeman says some of the genetic testing will be done at the National Institutes of Health, NIH (many of the children on the HH Support Group have already had this done on their blood). However, the RCH research will build on these data by testing other genes (to be conducted at Harvard, Boston) and testing of the tissue, which is where the Melbourne researchers believe they have the best chance of finding something. Early data from the Melbourne research have been published in the January
2001 issue of Neurosurgery (click here
to read a copy). A larger surgery outcome paper is in press in an Epileptic
Disorders supplement, another paper is in press in Neurology, and a
surgical technique paper is currently being considered by another journal.
Dr Kore Liow's Study at NIH In 1999 a group of HH families travelled to the National Institutes of Health (NIH) in Bethesda, Maryland to participate in one of the most comprehensive research projects ever conducted into the HH condition. The research was being conducted by Dr Kore Liow, who was until recently Clinical Associate at the NIH. Below is an excerpt of a letter sent to the HH Group by Dr Liow describing his study. Dear Families Gelastic seizure is indeed a rather rare seizure, even at a national referral center like the National Institutes of Health. Because of its rarity, doctors often missed the diagnosis. Even in cases where the condition is diagnosed, doctors often do not know what to do with it. We have in recent years seen quite a number of cases and, in conjunction with the National Human Genome Research Institute, have been able to link some of the hamartoma to a newly described genetic syndrome. It is still not known how frequently the hamartoma is inherited as this genetic syndrome. Because of the paucity of knowledge about this disease, we would like to see as many of these gelastic patients as possible. By conducting further testing, like special MRI, PET, SPECT, EEG and genetic testing, we could learn more about this disease to disseminate the information to neurologists worldwide. This will in turn enhance our ability to make a correct diagnosis, know the most effective treatments and be able to offer them to our patients. This will be the first time this disease is being studied in this scale and magnitude and the scientific findings will not only be significant to HH but may also help us to understand other generalized seizure disorders. These are the tests that we will be conducting at NIH: GENETIC BLOOD TESTS: to look for chromosomal mutation leading to the development of HH. I do not believe anyone else has looked at this. The mutation was discovered by Dr. Biesecker here at the NIH who will be doing the genetic studies with us. This will be extremely important in understanding the disease and could be the first step to finding a cure in the future. Like most diseases, finding out how it happens is often the clue to finding how to treat it or to prevent it. GENETIC WORK UP: including a detailed family history as well as a SKELETAL X RAY of the hands and feet if indicated. The development of HH is coupled to the development of fingers and toes during the 6th-7th week of gestation pregnancy. There is evidence that the two organ system may be affected together in children with the mutation leading to HH. It is not known how frequently the mutation exist in patients with HH and if there is another different mutation leading to the same HH but without the other anomalies. These findings will be significant in the understanding of HH. NEUROPSYCHOLOGICAL EVALUATIONS: these will be conducted to classify the type of cognitive deficits present (if any) in HH children and monitor their progress over the years. We would like to work with your local providers to help manage your child in this area. I have sporadic calls telling me that one antidepressant works better that the next, so why don't we centralise everyone and see if we can make any sense out of it. There is currently little data available for managing behavioral problems in these children and I feel it is time we conduct a systematic evaluation and release the relevant data. MODIFIED VIDEO-EEG: This will be different from previous EEGs in that it will have different leads specifically placed to try to detect gelastic seizures from HH. Apart from invasive EEG like depth (surgical) electrodes, we still do not have accurate methods to detect gelastic seizures and that may be why some of your children are initially diagnosed with some other seizures/disorders or even a psychiatric condition. This will not directly benefit your children but if the data is helpful, it will help physicians in the future to make the right diagnosis earlier without dismissing it as a mere psychiatric or behavioral problem. MRI STUDIES LOOKING FOR CHEMICAL RECEPTORS in HH and the brain. This will not be like a regular MRI, but specially designed to look for a deficiency of chemicals and their receptors in HH compared to the rest of the brain. We are interested in seeing if HH fires because it lacks certain calming chemicals. We are not sure how this could help but if there is a specific chemical missing, then we could concentrate on using or designing a specific drug to replace the missing chemicals. We would also be very interested in obtaining any HH tissues from resection to further study this. ENDOCRINOLOGIC EVALUATIONS: Some HH kids have precocious puberty and some do not. Could the hormones contribute to the seizures or vice versa? Could there be a hormonal therapy that we should explore? These are the questions that prompted us to pursue this. We will be obtaining hormonal blood levels before and after seizures. Your stay at NIH will be something like this: Day 1: advanced MRI study, hands and feet X ray, blood draw for genetic and hormonal
studies, history and exam We feel that this study is of such importance in its contribution to the understanding of this disease and possibly other seizures, we encourage more participation from your group. We have close to 10 people who are scheduled for June/July 1999 and expect more once we send out NIH recruitment letters to all epilepsy centers worldwide. The more people that we are able to study, the better the statistics and stronger the data, and we will already have won the first step of the fight against gelastic seizures. Kore Liow, MD In all, more than a dozen HH families underwent testing at the NIH during 1999 as part of Dr Liow's study. On 22 June 1999, Dr Liow wrote the following to the HH Group: We have seen about 10-15 cases of HH with
gelastic seizures over the years referred from the other study groups and now, with the
participation from your group, we will have the experience of seeing close to 30 cases.
This is again an extremely rare form of epilepsy; neurologists in their whole career may
see only one or two cases. Our preliminary assessment is leading us to the following
observations: Kore Liow, MD In 2000, Dr Liow left NIH to become Medical Director of the Comprehensive Epilepsy Center and Neurological Laboratory at Kansas University. Here he hopes to continue the important research into HH that he began at NIH. WATCH THIS SPACE for the latest from Dr Liow!
|
