Author: John F. Kerrigan, MD, Director, Hypothalamic Hamartoma Program, Phoenix Children's Hospital
What Have We Learned About Treating HH and Epilepsy? Part II
Surgical Treatment of HH Associated with Epilepsy
There have been several important clinical research publications over the past decade that report the results of the various surgical therapies that are now available for patients with hypothalamic hamartomas (HH). I have selected 6 studies that I regard as the most informative, and summarized them in the Table below. The references for each of these studies are listed at the end of this article.
Each column lists an individual research study. The very first column identifies the feature from each study that is being compared. For example, the specific surgery for each study is identified in the second row, the number of patients in each study is identified in the next row, and so on. This Table focuses on the “Efficacy” (or success) of each study for controlling seizures associated with HH, reporting the percentage of patients who are completely free of seizures (100% Seizure-Free) and also the percentage of patients who were not seizure-free, but had at least a 90% reduction in the number of seizures (>90% Improvement). These two outcomes are usually thought of as treatment “success” for epilepsy surgery, although admittedly our goal is to achieve complete (100% Seizure-Free) seizure control for as many patients as possible.
In these published research studies, outcome for seizure control was assessed when the patients were at least one year out from surgical treatment. For patients treated with gamma knife radiosurgery, treatment successs is measured after 2-3 years, since the effectiveness of the gamma knife technique for controlling seizures is delayed by 6-24 months. Lastly, 100% seizure control at one year after surgery may not mean seizure-free forever. As with other types of epilepsy surgery, a few patients may relapse with seizures years later, for reasons that are not well-understood.
For comparison purposes, the Table lists only one possible complication of surgery, short-term memory loss (always an important issue for patients with HH). Other complications are possible with any of the available treatments, and should be discussed in detail with the team of doctors. The Table also provides information on the average age of the patients treated in the study, and the average volume (or size) of the HH lesions belonging to those patients.
The first study in the Table (Palmini) is largely of historical interest, since it relates the success rate of surgery prior to the development of other approaches or interventions (which are represented by the next 5 studies in the Table). Accordingly, it provides a frame of reference for more recent studies. Notice that only 15% of patients in the Palmini study (in which all HH patients were treated with a pterional [subtemporal or subfrontal] approach) became completely seizure-free, and that this percentage is substantially higher in all the subsequent studies. Basically, the pterional approach for all HH patients is the “old way” of doing HH surgery, and the various types of surgery listed under the subsequent studies represent the “modern era”. (The pterional approach is still the most appropriate surgical approach for some patients with HH, specifically those with Type I lesions [according to the Delalande classification], in which the HH is attached to the underside of the hypothalamus.)
Many readers will be tempted to look across the “100% Seizure-Free” row in the Table and select the type of surgery with the highest success rate as the best choice for themselves or their family member. However, it is very important to stress that each of the operations (Type of Surgery) noted here is appropriate for different groups of HH patients. That is, no one treatment technique is suitable for all HH patients. Another way of making the same point is to say that treatment must be individualized to the needs and circumstances of each unique patient.
Reinforcing this idea, note that the studies shown in the Table did not treat identical groups of patients, and in fact, in many ways they are quite different. To give an example, in the 2006 study on transcallosal resection published by Ng and colleagues, the average age of the patients was 10 years, and the average size of the HH lesions was 4.0 cm3. In comparison, in the 2007 gamma knife series reported by Regis and colleagues, the average age of the patients was almost 18 years, and the average lesion size was 0.7 cm3 (more than 5 times smaller). In other words, one cannot make an “apples to apples” comparison between the various studies. Each one must be judged on its own merits.
As noted in Part I of this column (available here), there are two very important factors that determine which operation or surgical approach is best. These are 1) the stability of the patient (Are the symptoms stable, or getting worse over time?), and 2) the surgical anatomy as determined by the HH Type (Delalande HH Classification; see references in Part I of this column, available here).
Also, as noted previously, there are no controlled or randomized studies that prove which surgical treatment plan or approach is better. Undoubtedly we will learn more and change our thinking with experience and further research. However, based upon our clinical experience with over 150 patients, and the published research studies that are available (including those shown in the Table), the Barrow HH Program uses the following treatment algorithm (or roadmap) for considering the best treatment options for each patient (See Figure below).
It is impossible to consider the individual circumstances for every HH patient in a brief column of this type. One hallmark feature of HH is that there is a tremendous diversity from one patient to another. My comments here are to provide a framework so that each HH patient or family can be a little more knowledgeable and informed as they discuss treatment choices with their own team of doctors.
Delalande O, Fohlen M. Disconnecting surgical treatment of hypothalamic hamartoma in children and adults with refractory epilepsy and proposal of a new classification. Neurol Med Chir (Tokyo) 2003;43:61-68.
Kameyama S, Murakami H, Masuda H, Sugiyama I. Minimally invasive magnetic resonance imaging-guided stereotactic radiofrequency thermocoagulation for epileptogenic hypothalamic hamartomas. Neurosurgery 2009;65:438-449.
Ng Y-t, Rekate HL, Prenger EC, Chung SS, Feiz-Erfan I, Wang NC, Varland MR, Kerrigan JF. Transcallosal resection of hypothalamic hamartoma for intractable epilepsy. Epilepsia 2006;47:1192-1202.
Ng Y-t, Rekate HL, Prenger EC, Wang NC, Chung SS, Feiz-Irfan I, Johnsonbaugh R, Varland MR, Kerrigan JF. Endoscopic resection of hypothalamic hamartomas for refractory symptomatic epilepsy. Neurology 2008;70:1543-1548.
Palmini A, Chandler C, Andermann F, Costa Da Costa J, Paglioli-Neto E, Polkey C, Rosenblatt B, Montes J, Martinez JV, Farmer JP, Sinclair B, Aronyk K, Paglioli E, Coutinho L, Raupp S, Portuguez M. Resection of the lesion in patients with hypothalamic hamartoma and catastrophic epilepsy. Neurology 2002;58:1338-1347.
Regis J, Scavarda D, Tamura M, Villeneuve N, Bartolomei F, Brue T, Morange I, Dafonseca D, Chauvel P. Gamma knife surgery for epilepsy related to hypothalamic hamartoma. Semin Pediatr Neurol 2007;14:73-79.
Schulze-Bonhage A, Trippel M, Wagner K, Bast T, Deimling FV, Ebner A, Elger C, Mayer T, Keimer R, Steinhoff BJ, Spreer J, Fauser S, Ostertag C. Outcome and predictors of interstitial radiosurgery in the treatment of gelastic epilepsy. Neurology 2008;71:277-282.