Are therapies for HH changing?
Treatment for hypothalamic hamartomas (HH) have improved dramatically in the last 10 years. There is no cure yet, and it’s important to discuss all options with your health care team, including likely benefits, possible risks, and long-term impact.
Sometimes families don’t have specialists in HH close by and they may need to travel to another medical center for surgery or treatment. When this is needed, make sure you also have a good relationship with the doctors in your local area so they can help with follow-up care and treatments.
What treatments are available for HH?
Not all treatments are available at all epilepsy centers. Sometimes recommendations are based on the treatments available at each facility. You may need to look around at different centers to learn about these.
Treatment options for hypothalamic hamartomas and the associated seizures currently include:
- Seizure medications or antiepileptic drugs
- Transcallosal anterior interforniceal approach
- Transventricular endoscopic resection/disconnection
- Orbitozygomatic approach
- Stereotactic radiosurgery or gamma knife surgery (GKS)
- Stereotactic thermal ablation
- MR-guided stereotactic laser thermoablation
- Interstitial radiosurgery
- Staged surgical procedures
- Combination of approaches
- Other treatment options
Are seizure medications helpful in treating HH?
Most doctors require individuals with HH to start a seizure medication, since this is the least invasive (doesn’t require surgery).
- Seizure medications may help control some types of seizures, yet seizure freedom or even good seizure control can be hard to obtain. Less than 5% of people with HH become completely seizure free with medication alone.
- There does not seem to be one specific medicine that stops or even reduces the number of seizures long term.
- Seizure medicines can be helpful in controlling other seizure types (absence, complex partial, and generalized seizures) that often occur with HH.
- Deciding which drug to try first and whether to try one drug at a time, or more than one at a time, is difficult. The choice of medicines will depend on the type of seizures the person is having, side effects, and other problems that may be happening.
- Using seizure medicines in someone with HH follows the same principles as with other types of epilepsy.
- It will take a few weeks or more for a medicine to reach a stable state, so people need to give the medicine time to work.
- Some side effects that happen early on will go away on their own. Others may not go away or could cause other problems, meaning the person won’t tolerate the medicine.
- Doses are usually adjusted or changed slowly over time to lessen potential side effects.
- Some individuals may have a “honeymoon effect” where the medicine seems to be working and then loses its effect for no clear reason.
- Some parents have reported that their child’s seizure frequency changes in cycles. They report days or weeks of high frequency followed by days or weeks of very few seizures, regardless of medication dosage.
- People should not stop or lower a seizure medication on their own - this could make seizures worse and cause long or repeated seizures called status epilepticus.
When should surgery be considered?
When considering surgery, it is important to consider all the benefits and risks. Each person (or family) should make an individual decision about whether surgery is right for them.
- For infants and young children with only gelastic seizures, the decision to “watch and wait” may be the most comfortable decision for some families.
- However, studies show that 50% of children with only gelastic seizures in their early years develop the deteriorating form of HH.
- These children will eventually have more developmental, learning, and thinking problems.
- At least 3 out of 4 children will develop other seizure types in their lifetime.
- Further research needs to be done comparing the outcomes of individuals who choose to intervene early versus those who delay it.
What tests are done before surgery?
People with refractory epilepsy (epilepsy that doesn’t respond to medicines) need thorough testing. Before surgery for HH, the following tests are generally done.
- Detailed information about seizures, their location, severity, and frequency
- The type and size of hypothalamic hamartoma
- Neurospcyholgocal (cognitive) testing
- Neurobehavioral screening
- Endocrone (hormonal) tests
- High quality magnetic resonance imaging (MRI), using a specific HH protocol
- Electroencephalogram (EEG) monitoring, often a 24-hour video EEG may be enough to evaluate seizures.
- Other imaging tests that can help look at brain function, such as fMRI, and the areas where surgery may be done.
Which surgery is right for me?
There is no right surgery for everyone. The importance of making individual decisions about surgery can’t be overemphasized.
- Each person’s age, developmental stage, seizure profile, risks, surgical resources, and neurosurgeon's experience should all be taken into consideration.
- Several successful surgical approaches now in use allow for complete or partial removal or disconnection of an HH. With these advances, many HH treatment centers are recommending early intervention based on changes in quality of life after these procedures.
What types of surgery can be done?
This approach is often the best for a larger hamartoma. Most HHs are attached to one or both sides of the hypothalamus and may extend into another section of the brain (the third ventricle)
- During surgery, the hamartoma can be removed or the connections in that area interrupted without injuring other important brain areas.
- Improvement with this approach has been very promising. Fewer seizures, improved behavior (with less aggression or rage), better concentration, and improved mood have been reported.
- Possible complications include injury to the hypothalamus, short-term memory problems, increased appetite, and weight gain.
- Rare problems include sleep problems, temperature changes, or changes in hormone function. This is called panhypopituitarism, which means lower levels of several pituitary hormones, including thyroid and growth hormone. Hormone replacement therapy may be needed.
This type of surgery has proven to be a good treatment for smaller HHs that are attached to only one wall of the third ventricle.
- The center of the hamartoma is removed. If possible, the part that connects with the hypothalamus is carefully separated.
- Some surgeons believe that completely disconnecting the HH from the surrounding tissue is just as effective as surgery that completely removes the hamartoma.
- Improvement in seizures with this approach is similar to the transcallosal approach. Significant improvements in behavior have also been reported.
- This surgery is not as invasive and people are usually in the hospital a shorter time.
- Complications are similar to the transcallosal approach.
Before the approaches described above were used, the HH was most often surgically removed by approaching it from below. This is called the orbitozygomatic or pterional approach.
- Now, this approach is usually used for HH lesions that can’t be reached from above.
- For some lesions, a combination of approaches may be needed to completely remove the HH.
Stereotactic radiosurgery aims high-dose radiation at the HH tumor from many directions. This exposes normal tissue around the HH to only very small amounts of radiation.
- GKS has been used worldwide for other brain tumors and abnormalities. It’s a good way to reach small lesions that are deep in the brain and hard to reach with open surgery.
- This approach does not require making an opening in the skull, so it avoids side effects of an open surgery and removing the hamartoma.
- It does not cause any pain or sensation, except possible discomfort from placing a frame on the head.
- The side effects of radiosurgery are believed to be rare, short-term, and usually very predictable.
- A disadvantage of radiosurgery is that results are not seen right away. It may take 6 to 18 months (for some, even up to 3 years) to see the full effects of the treatment.
- Sometimes, repeat radiation may be needed to get the best effect. If GKS doesn’t work, standard surgery may still be an option.
Stereotactic thermal ablation is a technique where a wire is placed into the HH tissue using special equipment, and the probe is heated up. This process physically ablates or destroys the hamartoma tissue.
- A Japanese study of 19 people reported 68% of them were seizure free at one year with no long-term complications. Most patients also reported improved cognition without any adverse impact on short-term memory.
A newer approach involves using an MRI to guide laser thermal ablation in almost real time.
- Laser is a minimally invasive type of neurosurgery that creates a 2 cm diameter thermal lesion to destroy the HH.
- The advantage of this technique is that surgeons can use MRI to help control and properly place the probe, and deliver heat to the right area. The heat travels a shorter distance than in other approaches.
- The effect is immediate and, because it is less invasive, the hospital stay is also shorter.
- It has a low complication rate.
- Some disadvantages are:
- The procedure can’t be done on all lesion sizes or locations.
- It’s a new technology and we are still learning how well it can work.
- How the brain responds to heat from the laser is still not well understood.
- Early studies are promising. At one center that performed 62 ablations on 49 patients, 83% patients were free of gelastic seizures. Ongoing studies of people with longer follow-up times are critical.
This method of treating HH puts radioactive seeds in the hamartoma tissue. Some people may need a second dose of the radioactive substance.
- It may take 8 weeks for a change in seizures to be seen after this procedure.
- In a study of 24 people in Germany, 38% of them were seizure free one year later and another 17% had improved significantly.
- Cerebral edema (swelling), headaches, and fatigue may be seen after surgery.
“Giant” HH lesions have a volume greater than 4 cm3. People with very large hamartomas have a higher risk of epilepsy and cognitive problems. How to approach these surgically can be very challenging.
- One group of surgeons has proposed treating these cases with two surgical teams operating at the same time. One team approaches the HH from above and another approaches from below.
- A “staged” approach may be considered where two surgeries may be done a week apart.
Is a second operation ever needed?
Sometimes, the first surgery doesn’t help. A second operation may be needed. The second surgical technique might be different then the first. Surgeons may recommend a combination of approaches.
What are the risks of surgery for HH?
Complications of surgery fall into 3 areas:
- Acute risks relate to the surgery itself, for example blood loss, swelling of the brain, short term memory loss, or a hormonal problem (diabetes insipidus) that causes extreme thirst and frequent urination.
- Intermediate side effects, such as seizures coming back, may occur if the HH wasn’t fully removed or treated.
- Long-term risks could occur, such as seizures arising years after surgery or mental health issues.
What follow-up should occur after surgery?
After any type of surgery for epilepsy, people should have regular follow-up care with their epilepsy team.
- The health care team may order EEG, MRI, and other brain scans and test the person’s neurological, behavioral, or neuropsychological functions.
- These are usually repeated at specific time points after surgery to determine short- and long-term effects of surgery and if treatment changes are needed.
Are any surgeries specifically recommended to avoid?
Corpus callosotomy has not been helpful for people with HH.
What surgeries are on the horizon?
Previously studied as a treatment for other types of epilepsy, studies are being done to see how focused ultrasound can treat HH. One study at the Univeristy of Virginia is treating adults. Another at Nicklaus Children’s Hospital in Miami is testing this technique in children.
- This is a noninvasive technique, which means that an open surgery is not done.
- Concentrated ultrasound waves are used to destroy the hamartoma tissue.
- Serious side effects are not anticipated, as the technique is noninvasive.
- Since the hypothalamus produces and monitors hormones, endocrine function may be changed if normal hypothalamus tissue is affected too.
Other treatments, including dietary therapy (such as the ketogenic diet), devices like vagus nerve stimulation (VNS), and deep brain electrical stimulation (DBS), may be tried. Not enough information is available to tell how well these treatments work in children with HH.