What’s new in brain tumor-related epilepsy?
The Upcoming SIG
The upcoming SIG at the AES is in Washington DC 2017; There was a new SIG at the ACNS started in Phoenix 2017. There was a recent symposium at the AANS in Los Angeles (Apirl 2017). There is a sunrise session coming up at the SNO in San Francisco, November 2017. Several reqests for invited reviews on TRE, deriving from symposia at major meetings, are currently in process. The green journal supplement is still open as is the AAN practice parameter project.
Article Summaries for Non-Specialists
Objective – The ketogenic diet has been used with success for refractory epilepsy (when anti-epileptic drugs are unable to effectively stop seizures). Administration of the ketogenic diet leads to formation of ketone bodies – normal brains cells can use ketone bodies as an energy source but tumor cells cannot. Hence, in addition to the role of the ketogenic diet in epilepsy, there may also be a role of the diet in shrinking the tumor. The authors of a recent study asked whether the ketogenic diet is beneficial in one kind of brain tumor called glioma in mice.
In this model, glioma cells were implanted into the brains of mice (mice were anesthetized and care was taken so that the mice do not feel undue pain). KetoCal, a commercially available ketogenic diet for pediatric epilepsy patients was used, and was compared to the standard diet. If the ketogenic diet is found to be useful in mice, it is expected that it will be tested in a subset of brain tumor patients. But it is unlikely that it will be tested without an adjuvant therapy. Hence, in this study, the authors observed the efficacy of KetoCal in glioma in mice along with radiation. more...
Understanding Brain Tumor-Related Epilepsy
Epilepsy is rather common in people with brain tumors – seizures can be the presenting symptom (i.e., seizures may be the reason an individual with a brain tumor seeks medical help) or may occur later in the course of progression of the brain tumor. The incidence of seizures depends on the type and location of the brain tumor. For example, in certain kinds of slow-growing tumors, seizures may be seen in as many as 80% of the patient population.
Brain tumors can be primary (tumors that begin in the brain or spinal cord) or secondary (tumors that reach the central nervous system from another part of the body). Brain tumors can also be classified as benign (slow-growing masses that have a defined edge and do not usually spread to other parts of the body) or malignant (tumors that grow quickly, have hard-to-define edges and do usually invade the surrounding tissues). more...
The occurrence of spontaneous seizure (i.e. epilepsy) in individuals with brain tumors is rather common, but mechanisms underlying it are not well understood. Presently, tumors assume the forefront of treatment, whereas seizures are treated as something of an afterthought. As a result, there are times when removal of tumors does not necessarily mitigate seizures. One reason for this could be that the peritumoral tissue (tissue around the tumor) is also epileptogenic i.e. capable of producing seizures, but this is not visualized by MRI imaging. This would mean that removal of tumor as seen by MRI may or may not provide complete tumor resection.
A novel way of understanding the complexities of brain tumor-related epilepsy is systems biology. Simply speaking, systems biology is a way of approaching a disease from various directions, using various techniques. For example, in brain tumor-related epilepsy, one could look at the electrophysiological and genetic profile of tumoral tissue and compare it with peritumoral tissue. This approach would give us more information than a MRI alone would, and is gaining popularity in treatment of tumor-related epilepsy.
Dietary options for brain tumor-related epilepsy
Dietary therapies for people with epilepsy have been around for a while. The ketogenic diet (a diet consisting of high fat, low carbohydrate and adequate protein) has been shown to be beneficial in individuals with refractory epilepsy i.e. epilepsy that does not respond successfully to medication. A case study was published in 2010 where in an individual with glioblastoma multiforme (GBM), the ketogenic diet was added to the standard therapeutic regimen. In this case, there was a drastic shrinkage of the tumor tissue after being on the ketogenic diet for two months. Although this is only one patient, other reports have suggested the usefulness of dietary therapies in brain tumors as well.
Given that dietary therapies have been proved to be useful in both epilepsy and brain tumors, it makes sense to examine whether it could be beneficial in brain tumor-related epilepsy. Actually, this is an area of active investigation – the hope would be that dietary therapies could reduce shrink the tumor and reduce seizure frequency.
A potential marker for seizures in individuals with brain tumors
Patients with low-grade gliomas can present with seizures, but why some brain tumors are associated with seizures is not fully understood. One hypothesis is that genetic factors can underlie this phenomenon.
Currently, no marker exists that can predict whether a patient with brain tumor will have seizures. A recent study showed that a protein called RINT1 (short for ‘RAD50 interactor 1’) could be a potential marker, because patients that had a high expression of RINT1 were more likely to present with seizures than those that had low expression of RINT1 protein.
Although more research needs to be done, this study is exciting because it may give clinicians the tools to predict who with brain tumors will present with seizures. For scientists, too, this study gives a potential genetic mechanism to understand the reason why epilepsy sometimes occurs with brain tumors.