Synchronicity – The evolution of understanding of Hypothalamic Hamartoma

Author - Dr. Harold Rekate

Synchronicity is the concept that multiple events or processes can occur simultaneously that affect each other but result from entirely different causes. It relates to coincidence. I first learned about the concept from the song and album of that name by the Police. It would have been better had I known about this important concept by studying the psychologist who developed the concept, Carl Jung. The evolution of thought and, indeed, hope for hypothalamic hamartomas has been extraordinarily rapid in a way that is hard to imagine. This evolution would not have been possible if weren’t for the nearly simultaneous development of the internet, widespread availability of magnetic resonance imaging, innovations leading to safer neurosurgery, the extraodinary insight of one neurosurgeon and the remarkable courage of affected patients and their families. This discussion is a brief recounting of that history.

My personal experience with HH began over 35 years ago when I was a resident and when CT scan was available in only a few US cities and not in Cleveland where I was training. MRI was a technique that was being used in basic science labs to identify components of chemical mixtures and there was no hint that it would be useful in the imaging of the brain. The first case that I became involved with was a young girl with precocious puberty whose HH was discovered after the CSF around the brain was removed and replaced with air to show the mass. We assumed that it was a tumor and approached the mass underneath the brain. At surgery it was clear the we would not have been able to discern what was mass and what was the native hypothalamus. We sent the biopsy for frozen sections where it was read as normal hypothalamus. My professor instructed me to close up as there was nothing to do. Generally, that approach was the state of the art of neurosurgery until the 1990s and unfortunately, it is still happening to this day.

The first advance in our understanding of this condition related to the great advances in neuroimaging. The first CT scans were installed in a very few centers as of 1973. A small percentage of HHs could be seen if they were large enough to create distortion of the anatomy of the third ventricle, hypothalamus and optic mechanisms. It wasn’t until the general availability of MRI beginning in the mid-1980s. Even with MRI, small HHs are frequently missed unless specifically sought. At that time few neurosurgeons, neurologists or neuroradiologists were familiar with the syndromes associated with HH and therefore many were and some continue to be missed. At this point, making the diagnosis of hypothalamic hamartoma explained what was causing the problems but still did not lead to an answer to the sometimes devastating clinical condition of the sufferers.

As far as I can find, the first reports of successful resection of HHs come from the Hospital for Sick Children in Toronto. The first of these was a pedunculated hamartoma causing precocious puberty (1980 by R Humphries) and the second was for seizures (1981 H Hoffman). In both cases the surgical approach was performed by what is called a pterional approach from underneath the brain above the optic nerves. The description of the operation for the seizure related hamartoma was described as “we found the hamartoma below the optic nerve, could not see a difference between the hamartoma and the normal brain, the entire mass was removed and the patient did well.” This description did not give other neurosurgeons guidelines on surgical technique in this very sensitive location. At this point in our understanding, there was no certainty that the hamartoma could be resected without devastating deficits or the death of the patient. There was little faith at that time that successful removal of the mass would lead to significant improvement in the patient’s condition. Neurologists and neurosurgeons had little enthusiasm for attempted surgical treatment of these lesions. It remained for the group in Melbourne, Australia under Drs. Geoffrey Rosenfeld and Simon Harvey to study the anatomy of the hamartoma and its relationship to the vital structures within the hypothalamus and postulate that resection would lead to improvement in the patient’s condition. Dr. Rosenfeld studied what he has called the anterior interforniceal trans callosal approach and in 2001 published his first series showing 52% of patients treated via this approach were seizure free when followed for at least 30 months. This seminal work and the important role of Gamma knife therapy by Dr. Regis from Marseilles France showed that the hamartoma was distinct from the hypothalamus and was the cause of the seizures. Finally, there was real Hope for Hypothalamic Hamartoma sufferers.

This is where the internet comes into the story. Until the beginning of this millennium, the diagnosis of hypothalamic hamartoma was frightening and there was little that could be done. The internet made it possible to get a great deal of information in a short period of time. Unfortunately there was little information out there and even less that gave them significant hope. These desperate families seeking answers found each other creating the HHUGS website support group. They shared information with each other and when treatments became available that offered hope the word was out. Patients from all over the world found their way to either France or Australia for treatment.

As Dr. Rosenfeld’s numbers grew there remained a great deal of skepticism about the surgical management of these lesions. Acceptance of Gamma knife treatment was less controversial and soon it was being performed in a significant number of centers around the world. Professor Rosenfeld realized that for the majority of the world’s population, Australia was far from home and the numbers of affected families that could travel for his care was limited. His altruism had already been shown by his commitment to travel to underdeveloped countries and provide surgical care as a volunteer. He committed himself to training other centers in the techniques that he had developed. In 2002 and 2003, Dr. Rosenfeld traveled to several centers in Asia, Europe and the US to expand the availability of the procedure to a larger population of affected individuals. With the support of the Soeby family, one of the chosen sites was the Barrow Neurologic Institute in Phoenix where I was practicing at the time. He and I saw 11 families with children with intractable seizures and hypothalamic hamartomas and operated on five together that week. The results were remarkable. Since that time over 150 procedures have been done at the BNI and I have done six such patients and established a center at my current location at the Chiari Institute on Long Island. A high percentage of these patients found their way to HH centers by doing internet based searches.

Safe, successful resection of hypothalamic hamartomas is a great challenge because there is not a clear plain separating the very sensitive and vital areas of the hypothalamus and the hamartoma itself. For most of the patients, it is the development of frameless stereotaxis that makes it possible to define the limits of surgery in this condition. This new technology takes three dimensional information as seen on MRI scans and then creates a real time map of the inside of the brain similar to a GPS system for the car. It allows the surgeon using either microscope or neuroendoscope to know where he or she is operating at all times and to define the limits of surgery without visual clues. For many of our patients, successful surgery would be impossible without this new technology.

Advances in the minimally invasive neurosurgical procedures such as precise neuroendoscopy now makes it possible to actually remove these lesions in total using endoscopes that are only a few mm in diameter. This is especially important because as opposed to tumors that usually present with hydrocephalus (large ventricles) making neuroendoscopy easier. Instruments that facilitate this resection and in particular the Myriad device by the Nico Corporation have been developed particularly for this purpose.

The collection of a large number of patients in a few centers has lead to an explosion of knowledge not only on how to treat this lesion but also on the process of the development of epilepsy, the effect of epilepsy, and the effects of hormonal derangement on behavior and intelligence. With the privilege of caring for a relatively large number of patients with a rare disease comes a great responsibility. It is very unlikely that there will ever be again a center that will be able to accumulate such a large series of patients. Therefore, we are trying to spread the information to the neurologists and neurosurgeons to continue the work of Professor Rosenfeld in spreading the knowledge of the treatment of HH so that all patients with this condition can be treated appropriately. Taking our responsibilities to heart there are over 30 articles in scientific journals covering many different medical, surgical and basic science aspects of HH.

Hope for Hypothalamic Hamartomas (www.hopeforhh.org) was founded in 2010 by a small community of dedicated families who sought share lessons learned about HH and lessen the burden of new families diagnosed with this rare disorder. I am pleased to serve on the Hope for HH Medical Advisory Board with HH colleagues from around the world. The opportunity for us to exchange information will have a profound impact on the treatment and management of HH.

Each patient that has been treated for HH has been benefitted by the experiences gained by the treatment of patients who have gone before. We now know that the anatomic relationships of each of the HHs differ. When operating in the third ventricle, hypothalamic region you cannot work around corners but need a straight line of site whether using the endoscope or any of a variety of open surgical approaches. Some patients are best served by neuroendoscopic approaches. Some, especially young children with very large lesions require staged procedures utilizing 2 or even three approaches at different sittings. We have learned that total removal of the lesion gives the best chance of seizure freedom and that the effects of the HH on behavior, seizure type and cognition are often progressive in nature. For significantly affected individuals, early intervention is strongly recommended and total removal is the best treatment if it can be done with small risk.

Knowing that all the information is not yet available and that the surgical team will learn from his or her experiences in caring for your child or loved one is a very frightening process. It would be a great deal better to be the 10,000th treated patient than the 10th or especially the first. I never cease to be amazed by the courage shown by the patients and their families that have gone through treatment for this complicated condition.