Epilepsy: The Blood Test That Can Facilitate Diagnosis

Using continuous video-electroencephalogram (vEEG) recordings, researchers observed increased levels of interleukin-6 (IL-6) in the blood of patients with temporal lobe epilepsy (TLE) between and after seizures, but not in patients with frontal lobe epilepsy (FLE) or psychogenic nonepileptic seizures (PNES). The results suggest that immunological factors, such as IL-6, may be potential biomarkers to differentiate types of epileptic seizures and improve diagnosis.

Epilepsy is a neurological disorder characterized by recurrent and unpredictable seizures resulting from abnormal electrical activity in the brain. It is estimated that approximately 1% of the world's population is affected by this condition, which can vary in severity and manifestation.

The causes of epilepsy are diverse, including genetic factors, brain injuries, infections and other health problems.

Epileptic seizures can be of different types and locations, such as temporal lobe seizures (TLE) and frontal lobe seizures (FLE), which can be focal or generalized, each with its own clinical characteristics and specific implications.

Recent research suggests a two-way interaction between inflammatory processes and seizures. Inflammation can trigger seizures, and seizures, in turn, can intensify immune responses.

Immunological factors such as cytokines (proteins that modulate the immune response) and chemokines (which attract immune cells) play a crucial role in the control of communication and neuronal hyperexcitability that are characteristic of epilepsy.

A significant focus of research is interleukin-6 (IL-6), a pro-inflammatory cytokine that has been found to be elevated in the cerebrospinal fluid and serum of patients after generalized tonic-clonic seizures.

Generalized tonic-clonic seizures are a type of seizure in which the person loses consciousness and goes through two phases: an initial phase of muscle rigidity (tonic phase) followed by jerking or jerking movements (clonic phase). These seizures result from abnormal electrical activity in the brain and can leave a person feeling confused and tired after the episode.

Interleukin-6 (IL-6) is a cytokine, or signaling protein, involved in regulating the immune response. It plays an important role in fighting infections by promoting inflammation as part of the body’s response to injury or infection.

In addition to its functions in the immune system, IL-6 is involved in processes such as fever and the production of acute phase proteins in the liver.

Elevated levels of IL-6 are often seen in chronic inflammatory conditions, autoimmune diseases, and after epileptic seizures, indicating its importance in mediating systemic inflammatory responses.

Studies suggest that IL-6 levels increase not only during seizures but also in the interictal period (time between seizures) in certain types of epilepsy, such as temporal lobe epilepsy. However, the results are inconsistent, with some studies reporting an increase in IL-6 only in the postictal period (after seizures).

To investigate these discrepancies, researchers at Lund University in Sweden conducted a detailed study involving patients with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE), as well as psychogenic nonepileptic seizures (PNES).

Using continuous video-electroencephalogram (vEEG) recordings, they collected serum samples before and after seizures to measure the levels of 25 immune proteins, including IL-6.

During the examination, the EEG records the electrical activity of the brain continuously over several hours or days. Electrodes are placed on the patient’s scalp to capture electrical signals from the brain, which are recorded and analyzed.

While the EEG captures brain activity, a camera continuously records the patient’s behavior. This allows correlation between clinical events (such as seizures) and changes in brain electrical activity.

The patients were carefully monitored in a hospital setting, ensuring accuracy in identifying interictal and postictal periods.

In addition, the researchers considered factors such as seizure burden, epileptiform activity on EEG, brain pathologies observed by MRI, comorbidities, physical exercise, and use of anticonvulsant medications.

The results revealed that IL-6 levels were elevated interictally in patients with TLE, but not in those with PNES.

Following a seizure, IL-6 levels increased transiently in patients with TLE, but not in patients with FLE. In addition to IL-6, five other immunological factors showed significant postictal increases only in patients with TLE.

These findings suggest that immunological factors in peripheral blood may serve as useful biomarkers to differentiate between epileptic and non-epileptic seizure types.

The research also highlights the complexity of the immunological response in epilepsy, indicating that different seizure types may be associated with different immunological profiles, independent of other comorbidities.

Research on the relationship between immunology and epilepsy is constantly evolving, with significant potential implications for the diagnosis and treatment of the condition.

Identifying specific immunological biomarkers may help to personalize the clinical management of epilepsy, improving patients’ quality of life and opening the way for new therapies.

READ MORE:

Immune response in blood before and after epileptic and psychogenic non-epileptic seizures

Matilda Ahl,  Marie K. Taylor, Una Avdic, Anna Lundina, My Andersson, Åsa Amandussonc, Eva Kumliend, Maria Compagno Strandberge, Christine T. Ekdahla

Heliyon, Volume 9, Issue 3, e13938

DOI: 10.1016/j.heliyon.2023.e13938

Abstract:

Inflammatory processes may provoke epileptic seizures and seizures may promote an immune reaction. Hence, the systemic immune reaction is a tempting diagnostic and prognostic marker in epilepsy. We explored the immune response before and after epileptic and psychogenic non-epileptic seizures (PNES). Serum samples collected from patients with videoEEG-verified temporal or frontal lobe epilepsy (TLE or FLE) or TLE + PNES showed increased interleukin-6 (IL-6) levels in between seizures (interictally), compared to controls. Patients with PNES had no increase in IL-6. The IL-6 levels increased transiently even further within hours after a seizure (postictally) in TLE but not in FLE patients. The postictal to interictal ratio of additionally five immune factors were also increased in TLE patients only. We conclude that immune factors have the potential to be future biomarkers for epileptic seizures and that the heterogeneity among different epileptic and non-epileptic seizures may be disclosed in peripheral blood sampling independent of co-morbidities.