Introduction

Epilepsy is a chronic disorder in the brain that is characterised by uncontrolled neuronal activity leading to seizures.¹ Misconceptions about epilepsy contribute to stigma and discrimination, despite the fact that many individuals live normally.²

Cancer is caused by the uncontrolled growth of cells that can invade other parts of the body.³ Epilepsy and cancer are complex medical conditions in which patients and their families often bear a huge emotional burden. Such complicated relationships can be managed through open communication and by seeking professional help to build understanding and support.

The connection between epilepsy and cancer

Recognising the connection between epilepsy and cancer is important, as seizures can indicate the presence of brain tumours and cancer therapies can impact seizure occurrence. In adults, brain tumours are a major cause of epilepsy, which can have a significant impact on the quality of life and treatment outcomes of cancer patients.⁴

Epidemiology

Prevalence and statistics

Frequency of epilepsy in cancer patients

• Many patients with epilepsy tend to also have brain tumours. Seizure prevalence in these patients varies widely, ranging from 6% to 56%, depending on the study and patient population analysed⁵
• For example, in patients with high-grade gliomas (HGG), the seizure prevalence can be as high as 45% at some point during the end-of-life phase⁵

Risk factors

Genetic and environmental influences

• Genetic predispositions are significant factors in the development of epilepsy and specific forms of cancer. Specific gene mutations, including those related to tumour suppression and DNA repair, can increase the risk of developing both conditions
• Environmental factors, including exposure to carcinogens like radiation, can contribute to the development of brain tumours and consequently raise the likelihood of developing epilepsy⁵

How lifestyle and medical history play a role

• Smoking, poor diet, and excessive alcohol consumption can increase the risk of developing cancer, which in turn may lead to an increased risk of epilepsy if the cancer metastasizes to the brain⁵

Pathophysiology

How cancer can trigger epilepsy?

Tumours within the brain can disrupt the balance of neurotransmitters, such as glutamate and Gamma-Aminobutyric Acid(GABA), and enhance excitability, with an associated risk of seizures. In addition, tumours can cause structural changes in the brain, even changes in neuronal connectivity or synaptic plasticity, which predispose people to seizures. Further, reduced GABA inhibition aggravates this imbalance, adding to the vulnerability to seizures.⁶

Brain tumours as a cause of epilepsy

Due to their location and proliferation, gliomas are often linked to epilepsy. Seizures are more likely in frontal, temporal, and parietal tumours, affecting cognitive and sensory processes. Tumours can affect neurotransmitter release and receptor expression, causing seizures. As they develop and press on brain tissue, tumours also alter neuronal function, contributing to epileptogenesis.⁶

Diagnosis

Identifying epilepsy in cancer patients necessitates essential diagnostic tools like MRI, CT scans, and EEG to detect any structural irregularities and abnormal electrical discharges linked to seizures. Nevertheless, distinguishing between various types of seizures and the presence of similar symptoms in other conditions can pose a challenge, requiring thorough evaluations to ensure an accurate diagnosis.⁷

Challenges in Diagnosis

• Differentiating between seizure types can be challenging, especially in cancer patients, where neurological symptoms may overlap with those caused by the tumour or treatment. A detailed patient history and the use of advanced diagnostic tools are essential for accurate classification and effective treatment planning⁷
• Symptoms of seizures can overlap with other neurological or psychiatric conditions, such as migraines, transient ischemic attacks (TIAs), or psychogenic non-epileptic seizures (PNES). This overlap complicates the diagnostic process, necessitating comprehensive evaluations to distinguish epilepsy from other disorders⁷

Treatment and management

Antiepileptic drugs (AEDs)

Selecting the right AEDs, such as levetiracetam, is crucial for managing brain tumour-related epilepsy (BTRE) while minimising adverse effects. Adjusting AEDs and managing side effects are essential for optimal seizure control. For patients with uncontrolled seizures, potential add-on AEDs include lacosamide, perampanel, and valproic acid. ⁸

 Managing side effects and drug interactions

• While second-generation AEDs, like levetiracetam, are preferred for their reduced drug interactions and side effects, they can still cause psychiatric adverse effects such as depression and agitation⁸
• Despite valproic acid being effective, it is associated with low platelets that lead to excessive bleeding, which can be exacerbated by concurrent chemotherapy like temozolomide

Surgical options

When and why surgery is considered

• Surgical resection is often the primary treatment strategy for brain tumours and is also crucial for achieving seizure freedom. Gross total resection (GTR) is associated with significantly better seizure outcomes compared to non-GTR⁸
• Surgery is considered when seizures are refractory to medication or when the tumour is accessible, and its removal is likely to improve both survival and seizure control

Radiation and chemotherapy

Impact on seizure control

• Radiotherapy has shown positive effects on seizure control in low-grade glioma patients, with seizure freedom rates improving significantly post-treatment
• Chemotherapy, especially with agents like temozolomide and PCV (procarbazine, CCNU, and vincristine), also contributes to better seizure outcomes in glioma patients⁸

Strategies to minimise neurotoxicity

• To mitigate the neurotoxic effects of chemotherapy and radiotherapy, it is crucial to tailor treatment plans carefully, considering the patient's overall health, tumour type, and seizure history⁸

Holistic and multidisciplinary care

Importance of a comprehensive treatment team

• Collaboration among neurologists, oncologists, neurosurgeons, and supportive care specialists is essential to effectively meet the diverse needs of patients with BTRE. This approach guarantees comprehensive management of the patient's condition, encompassing tumour control, seizure management, and overall improvement in quality of life⁸

Integrating supportive therapies and palliative care

• Supportive therapies, such as neuropsychological support, physical rehabilitation, and palliative care, are crucial in enhancing the quality of life for patients with BTRE. These therapies are effective in managing symptoms, alleviating stress, and offering comprehensive care that caters to both physical and emotional well-being⁸

Prognosis

Living with both conditions

Quality of life issues

Managing both conditions often requires robust support systems, including psychological support, social services, and a multidisciplinary medical team. Effective coping strategies may include regular consultations with mental health professionals, access to social workers and support groups, and patient education to empower individuals to manage symptoms and treatment side effects effectively.⁹

Long-term outlook and survival rates

Research indicates that epilepsy in patients with certain types of cancer, such as glioblastoma (GBM), may influence survival outcomes. Patients presenting with epileptic seizures tend to have a longer median survival compared to those without epilepsy, suggesting that epilepsy still is an independent prognostic factor.⁹

Ongoing management

Long-term management of both glioblastoma and epilepsy requires regular monitoring and follow-up. The key aspects include:

• Neuroimaging: Regular MRI scans to monitor tumour progression
• Neurological assessments: Evaluations to monitor seizure control and make necessary treatment adjustments
• Blood tests: Monitoring for any side effects from the treatments⁹

Adjusting treatments over time is important:

• To optimise seizure control and minimise side effects by modifying AEDs
• To balance effectiveness with potential neurotoxic effects by tailoring chemotherapy and radiation therapy
• To intervene with surgical intervention when seizures exhibit resistance to medical management or in scenarios of tumour progression

Research and future directions

Current research trends

Recent studies focus on developing new antiepileptic drugs (AEDs) with improved efficacy and fewer side effects. Clinical trials explore novel therapies, like targeted molecular treatments and gene therapy, that are promising for epilepsy treatment, especially in cancer patients. Personalised medicine aims to tailor treatments based on genetic profiles, enhancing outcomes.^10,11

Technological advances

Advances in neuroimaging, like high-resolution MRI, improve epilepsy diagnosis, and treatment assessment. Personalised medicine integrates genetic data to customise therapy, reducing adverse reactions, particularly in cancer cases.

Future research needs

• Continued research into the genetic and molecular mechanisms of epilepsy is needed in the context of cancer. Identifying genetic markers and understanding molecular pathways can lead to the development of targeted therapies and preventive strategies
• Future research should focus on holistic care approaches that address both the medical and psychosocial aspects of living with epilepsy and cancer. This includes developing comprehensive care models that incorporate physical rehabilitation, psychological support, and palliative care to improve the overall quality of life for patients

FAQs

Does epilepsy get worse with age?

It's possible that it could get more serious, and the frequency of seizures will increase. However, it’s also possible that epilepsy gets better with age, whether it's due to natural changes in the body or improved treatment.¹²

Can cancer cause non-epileptic seizures?

For people with brain tumours, nonepileptic episodes can coexist with epilepsy.¹³

Summary

Addressing epilepsy and cancer requires a holistic and team-oriented approach that takes into account medical, emotional, and social aspects. Collaboration among healthcare professionals is essential to ensuring personalised treatment plans and holistic support. Ongoing research and increased awareness play a crucial role in advancing treatment options and enhancing outcomes. By actively engaging in education, advocacy, and support networks, individuals impacted by epilepsy and cancer can gain the tools and knowledge needed to navigate their challenges with greater effectiveness.