Reducing Seizures For Glioma Patients: A Significant Benefit From The Targeted Therapy Vorasidenib, Say Experts

Gliomas are a type of brain tumor that arises from glial cells, which support and protect nerve cells in the brain. These tumors can present with varying symptoms and arise from a range of gene mutations. These gene mutations have been recently discovered and have allowed for significant advancements in the treatment of patients with glioma.

One of the most significant developments in glioma treatment was the discovery of IDH (Isocitrate Dehydrogenase) mutations, which are found in many lower-grade gliomas. IDHs are specific genes that produce enzymes that help the cell to produce energy; therefore, their mutation potentially disrupts the cell’s normal function. Identifying these mutations is crucial for determining treatment options, including the use of drugs that directly inhibit mutated IDH genes, a treatment often referred to as “targeted therapy.”

Clinical manifestations of glioma vary according to each patient, disease degree, anatomical area in the brain, and overall health status. For instance, seizures can be the presenting symptom in approximately 70% of the patients, which can be both limiting and directly impact quality of life. To note, patients with IDH mutation are more likely to present seizures than those who don’t.

Why Do I Have Seizures?

To work properly and majestically command millions of circuits in our body, the brain has specific and precise connections between its cells. To simply exemplify, this means that whenever we give our brain a command, consciously or not, the impulse needs to travel through the correct prespecified “path” to culminate in doing what we want. However, if in the middle of the path this impulse encounters any obstacle, such as a brain tumor or swelling (edema), it will be precluded from moving forward and the energy (impulse) will dissipate or even evoke new waves of energy that can lead to a disarrangement in all of the other “paths”. To this dissipation or activation in unwanted areas, we call “seizures”.

“The IDH mutation drives gliomagenesis [tumor formation] in IDH mutant tumors, so is key in the process of the tumor starting and continuing to grow. In addition, the IDH mutation results in the formation and secretion of 2-hydroxy-glutarate (2-HG), which interacts with nearby nerve cells and is stimulatory to Glutamate Receptors on those nerves. The extra stimulation of the Glutamate Receptors is part of the mechanism for seizure activity in the brain tissue around the tumor”, explains Dr Herbert B. Newton, Neuro-Oncology Medical Director of the Brain Tumor Center at University Hospitals Seidman Cancer Center.

This is the reason why patients with brain tumors can primarily present with seizures or have them during the course of the disease. Thus, you should always watch for it. Even though it is common during the initial presentation or even during the treatment course, not all patients will have it.

Better Therapies, Better Seizure Control

With modern and targeted therapy that has been available for patients diagnosed with glioma in the last years, they can not only have a better prognosis, but also they can have substantial improvement in disease-related symptoms. Some medicines have clearer seizure benefits than others: for example, bevacizumab often reduces brain swelling (edema) and can lessen seizures in glioblastoma. Newer IDH-targeted drugs (like vorasidenib or ivosidenib) may potentially improve seizures in IDH-mutant gliomas.

“Vorasidenib is able to inhibit IDH mutant tumor cells, thereby reducing the growth potential of the tumor cells, and thereby the tumor mass overall. This is how the tumors are stabilized by the drug,” Dr. Newton explains.

“In addition, the excess stimulation and epileptogenic process are reduced in the nearby nerves. This is the basic idea for how Vorasidenib is able to reduce the seizure frequency and tendency for ‘Brain Tumor-Related Epilepsy’ in glioma patients,” further explains Dr. Newton.

Do I Need Treatment to Prevent Seizures?

This is an important step in the management of patients with brain tumors. Antiseizure medication therapy is indicated only for patients who have experienced a seizure and for those who have a history suggestive of previously unreported or unrecognized seizure activity due to a brain tumor.

On the other hand, prophylactic antiseizure medications are generally not recommended for patients with a primary or metastatic brain tumor and without a history of antecedent seizure.

Whether you need an anti-seizure medication should be extensively discussed by your healthcare team to offer you the best approach.

Importantly, never change seizure medication dose or frequency if not advised by your doctor. This action can precipitate seizure recurrence.

Tips For Day-To-Day Seizure Safety

• Keep a seizure diary: Note date/time, length, triggers, and any missed doses.
• Awareness: make sure that your loved ones and people who live close to you are aware of your condition so they can properly help you in an emergency.
• Take medicines on time. Use reminders (mobile App) or a pill organizer.
• Sleep and hydration help; limit alcohol and avoid recreational drugs.
• Driving & safety: Follow local laws about driving after seizures. Use extra caution with heights, water (showers > baths), and heated appliances.

Ask Your Doctor

• Is the presence of a seizure an indicator of the worst prognosis?
• Will target therapy control my seizures?
• I didn’t have a seizure, but I am afraid of having one. How can I prevent it?
• For how long will the seizure treatment take?.
• Am I allowed to drive if I have seizures?

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