What causes epilepsy?

Epilepsy occurs when the normal electrical signaling between the neurons in the brain becomes disrupted.  The exact causes for this disruption are varied and not completely understood, which makes it complex to diagnose (and treat).

On this page, you’ll learn about the six known causes of epilepsy and the diagnostic process physicians use to determine the underlying cause of a patient’s epilepsy.

HOW DOCTORS IDENTIFY THE CAUSE OF EPILEPSY

To help medical professionals around the world provide the best possible care to their patients, the International League Against Epilepsy (ILAE) introduced an updated tool for diagnosing epilepsy in 2017.

This system, called Classification of the Epilepsies, uses three levels to help physicians accurately diagnose an individual’s epilepsy: seizure type, epilepsy type, and epilepsy syndrome. As you can see from this graphic, it also emphasizes the importance of etiology, or causes, for each level, as this can determine which therapies are appropriate for a given patient.

The etiology of epilepsy is broken into six subgroups:¹

• Structural
• Genetic
• Infections
• Metabolic
• Immune
• Unknown

STRUCTURAL ETIOLOGY

A structural cause refers to brain abnormalities that are visible on structural neuroimages, such as an MRI. The underlying cause for this etiology can be acquired, genetic, or both.¹ A person can acquire structural damage through stroke or head trauma, or it can be caused by genetic mutations during brain development.

GENETIC ETIOLOGY

When a patient’s epilepsy is the direct result of a genetic mutation, they are considered to have a genetic etiology.¹ Epilepsies with a genetic cause can be extremely diverse and the underlying genes are not always known. It’s important to note that genetic epilepsy does not automatically mean that it was inherited, or passed down from a parent, meaning that the mutations can be present in an individual, but not their parents.² According to the ILAE, there is a 50% chance that a patient with a de novo genetic mutation will pass this trait down to their children.

INFECTIOUS ETIOLOGY

When a patient has an infection in which seizures are a main symptom, they are considered to have an infectious etiology. Infections are the most prominent cause of epilepsy worldwide. An infection can cause epilepsy by directly impacting the brain cells of the person, or by releasing toxins that causes inflammation and seizures. Some examples of infections which can lead to epilepsy are: ¹

• Cerebral malaria
• Encephalitis
• HIV
• Meningitis
• Tuberculosis
• Zika virus

METABOLIC ETIOLOGY

A metabolic disorder occurs when the process by which the body makes energy is disrupted or performs abnormally. Your body makes energy from the protein, carbohydrates, and fats in food that you eat. Chemicals break down the food into energy that can be used or stored. In some metabolic disorders, the abnormality affects the brain and increases the risk of epilepsy. Many metabolic epilepsies have a genetic origin (both inherited and de novo), though in extremely rare cases it can be acquired.

Identifying a metabolic cause can have important implications on how the epilepsy is treated.^{1, 3} The ILAE has identified eight metabolic epilepsies that are important to know about:

• Biotinidase and holocarboxylase synthase deficiency
• Cerebral folate deficiency
• Creatine disorders
• Folinic acid responsive seizures
• Glucose transporter 1 (GLUT1) deficiency
• Mitochondrial disorders
• Peroxisomal Disorders
• Pyridoxine dependent epilepsy/PNPO deficiency

IMMUNE ETIOLOGY

When your body recognizes a foreign agent (such as a virus), it protects itself by initiating an immune response. In some cases, your body may incorrectly identify itself as a foreign entity and begin attacking itself; if that autoimmune response causes you to have seizures, your epilepsy has an autoimmune etiology.^{5, 6} Examples of autoimmune epilepsy are Rasmussen’s encephalitis (also known as Rasmussen’s syndrome), limbic encephalitis, and GAD65 antibody-associated encephalitis.

UNKNOWN ETIOLOGY

As the name implies, epilepsies with an unknown etiology have a cause that is not yet known. In other words, a person can be diagnosed with epilepsy, but the physician cannot make a specific diagnosis beyond that. In some cases, this is because there is still much we do not know about epilepsy; in other cases, this may occur because the patient does not have access to all of the proper diagnostic tests in order for their healthcare professionals to make an accurate diagnosis.¹

References:

1. Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology Epilepsia. 2017 Apr;58:512-521.
2. Steinlein OK. Genetics and epilepsy Dialogues Clin Neurosci. 2008;10:29-38.
3. Pearson-Smith JN, Patel M. Metabolic Dysfunction and Oxidative Stress in Epilepsy International journal of molecular sciences. 2017;18:2365.
4. Lin Lin Lee V, Kar Meng Choo B, Chung YS, U PK, Kumari Y, Shaikh MF. Treatment, Therapy and Management of Metabolic Epilepsy: A Systematic Review Int J Mol Sci. 2018 Mar 15;19.
5. Geis C, Planagumà J, Carreño M, Graus F, Dalmau J. Autoimmune seizures and epilepsy J Clin Invest. 2019 Mar 1;129:926-940.
6. Husari KS, Dubey D. Autoimmune Epilepsy Neurotherapeutics. 2019 Jul;16:685-702.
7. Palace J, Lang B. Epilepsy: an autoimmune disease? Journal of Neurology, Neurosurgery & Psychiatry. 2000;69:711.