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WHAT IS EPILEPSY?

Epilepsy is a chronic neurological disorder characterized by recurrent, spontaneous seizures due to excessive and abnormal neuronal activity in the brain. Causes may include genetic factors, trauma, infections, and metabolic disorders.

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WHEN DOES EPILEPSY START?

Epilepsy can begin at any age, but most often manifests itself in early childhood and old age. The highest incidence is observed in children under 5 years of age and in adults over 65 years of age. Genetically determined forms of epilepsy most often manifest in infancy or childhood, while epilepsy caused by stroke or neurodegenerative diseases is more common in older people.

CLINICAL MANIFESTATIONS OF EPILEPSY

Epilepsy is characterized by different types of seizures, which can be classified as follows:

  • Focal seizures: begin in a specific area of the brain and cause local symptoms such as muscle twitching, changes in sensation, or changes in consciousness.

  • Generalized seizures: affect both hemispheres of the brain and include:

    • Absences (brief loss of consciousness)

    • Tonic-clonic seizures (loss of consciousness, convulsions)

    • Myoclonic seizures (sudden jerking)

    • Atonic seizures (sudden loss of muscle tone)

  • Status epilepticus: a dangerous condition characterized by prolonged or recurring seizures without recovery of consciousness.

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WHAT CHANGES IN THE BRAIN PRECURSE EPILEPSY?

The main pathological changes associated with epilepsy:

  • Hyperexcitability and hypersynchronization of neural networks

  • Loss of inhibitory GABAergic neurons, leading to an excess of excitatory signals

  • Neurodegeneration and gliosis, especially in the hippocampus (eg, mesial temporal sclerosis)

  • Impaired synaptic plasticity and neural network reorganization

  • Neuroinflammation and oxidative stress contribute to seizure propagation

WHAT AREAS OF THE BRAIN AFFECTED IN EPILEPSY?

The areas affected depend on the type of epilepsy:

  • Temporal lobe (most commonly involved in temporal lobe epilepsy)

  • Hippocampus (most often affected in mesial temporal lobe epilepsy)

  • Frontal lobe (associated with focal seizures)

  • Occipital lobe (may cause visual hallucinations and seizures)

  • Thalamus and cerebral cortex (in generalized forms of epilepsy)

OFFICIAL OPINIONS ON THE CAUSES OF EPILEPSY

Epilepsy is considered a heterogeneous disease with various possible causes:

  • Genetic factors: mutations in genes of ion channels (SCN1A, KCNQ2) and neurotransmitters

  • Structural abnormalities of the brain: congenital defects, tumors, injuries

  • Neuroinflammation and immune system disorders

  • Metabolic disorders: mitochondrial disorders

  • Infectious diseases: neuroinfections (viral, bacterial, parasitic)

  • Autoimmune epilepsy: associated with autoantibodies to neuronal receptors (eg, NMDA)

IMPORTANT GENETIC CHANGES IN EPILEPSY

Mutations were identified in the following groups of genes:

  • Ion channels: SCN1A, KCNQ2, CACNA1A

  • Neurotransmitter systems: GABRA1, CHRNA4

  • mTOR signaling pathways: TSC1, DEPDC5

  • Genes of synaptic functions and neuronal migration: RELN, DCX

THE ROLE OF INFLAMMATION AND CHRONIC INFECTIONS IN EPILEPSY

Inflammation and infections may play a key role in epileptogenesis by influencing neuronal excitability and brain damage. The main mechanisms are:

  • Activation of microglia and release of proinflammatory cytokines (IL-1β, TNF-α)

  • Astrocyte dysfunction promoting glutamate accumulation

  • Damage to the blood-brain barrier, allowing immune cells to enter

Scientific articles on the topic:

  1. Inflammation as a therapeutic target in epilepsy – discusses potential treatments targeting inflammatory pathways. Rana, A., Musto, A. E. The role of inflammation in the development of epilepsy. J Neuroinflammation 15, 144 (2018). https://doi.org/10.1186/s12974-018-1192-7

  2. The role of infection in the development of epilepsy - analyzes infections as risk factors for the development of epilepsy. Vezzani A, Fujinami RS, White HS, Preux PM, Blümcke I, Sander JW, Löscher W. Infections, inflammation and epilepsy. Acta Neuropathol. 2016 Feb;131(2):211-234. doi: 10.1007/s00401-015-1481-5. Epub 2015 Sep 30. PMID: 26423537; PMCID: PMC4867498.

  3. Viral infections and epilepsy - explores the bidirectional relationship between viral infections and epileptic seizures. Costa B, Vale N. Virus-Induced Epilepsy vs. Epilepsy Patients Acquiring Viral Infection: Unravelling the Complex Relationship for Precision Treatment. Int J Mol Sci. 2024 Mar 27;25(7):3730. doi: 10.3390/ijms25073730. PMID: 38612542; PMCID: PMC11011490.

ВЗАИМОСВЯЗЬ ЭПИЛЕПСИИ С ИММУННОЙ, МИКРОБИОМНОЙ, ЭНДОКРИННОЙ И МЕТАБОЛИЧЕСКОЙ ДИСФУНКЦИЕЙ

  • Иммунные механизмы: Аутоантитела, нарушение регуляции цитокинов

  • Микробиом: Нарушения кишечной микрофлоры, влияние на ГАМК-эргическую систему

  • Эндокринная система: Дисбаланс кортизола и половых гормонов

  • Метаболизм: Митохондриальные нарушения, дефицит глюкозного метаболизма

OFFICIAL METHODS OF EPILEPSY TREATMENT

  • Antiepileptic drugs (carbamazepine, valproate, lamotrigine)

  • Ketogenic diet

  • Vagal nerve stimulation (VNS)

  • Surgical treatment

ANTI-INFLAMMATORY AND ANTI-INFECTIOUS METHODS OF EPILEPSY TREATMENT (WITH BIBLIOGRAPHY)

Alternative treatments for epilepsy that target inflammation and infection are being explored:

  • Anti-inflammatory drugs: Ketorolac, anakinra (IL-1 inhibitor)

  • Antiviral agents: Valaciclovir for virus-induced epilepsy

  • Antibiotics: Minoccycline has neuroprotective properties

  • Probiotics: Help modulate the gut microbiome

ADDITIONAL SCIENTIFIC ARTICLES FOR MEDICAL SCIENTISTS AND PRACTITIONERS:

The Role of Inflammation in Epilepsy
Miller JW. Inflammation as a Target for Epilepsy Therapy: The Case of Natalizumab. Neurology. 2021 Nov 2;97(18):845-846. doi: 10.1212/WNL.0000000000012768. Epub 2021 Sep 14. PMID: 34521688.

Anti-Inflammatory Therapy in Epilepsy
Vezzani A, French J, Bartfai T, Baram TZ. The role of inflammation in epilepsy. Nat Rev Neurol. 2011 Jan;7(1):31-40. doi: 10.1038/nrneurol.2010.178. Epub 2010 Dec 7. PMID: 21135885; PMCID: PMC3378051.

Recent studies have highlighted the significant role of infections and inflammation in the development and treatment of epilepsy. Below are key studies and reviews that explore these connections and discuss potential therapeutic approaches:

INFECTIONS, INFLAMMATION, AND EPILEPSY

This comprehensive review examines various central nervous system (CNS) infections—including viral, bacterial, fungal, and parasitic—that may lead to seizures and epilepsy. The authors note that the risk of unprovoked seizures among survivors of CNS infections ranges from 6.8% to 8.3% in developed countries, with higher rates in resource-limited regions.

Vezzani A, Fujinami RS, White HS, Preux PM, Blümcke I, Sander JW, Löscher W. Infections, inflammation and epilepsy. Acta Neuropathol. 2016 Feb;131(2):211-234. doi: 10.1007/s00401-015-1481-5. Epub 2015 Sep 30. PMID: 26423537; PMCID: PMC4867498.

THE ROLE OF INFLAMMATION IN EPILEPSY

This article discusses how immune mechanisms and inflammation contribute to seizure generation. It notes that immunomodulatory and anti-inflammatory therapies—including adrenocorticotropic hormone (ACTH), corticosteroids, plasmapheresis, and intravenous immunoglobulin (IVIg)—have been used with varying degrees of success in the treatment of seizures and epilepsy.

Vezzani A, French J, Bartfai T, Baram TZ. The role of inflammation in epilepsy. Nat Rev Neurol. 2011 Jan;7(1):31-40. doi: 10.1038/nrneurol.2010.178. Epub 2010 Dec 7. PMID: 21135885; PMCID: PMC3378051.

INFLAMMATION AS A TARGET FOR EPILEPSY THERAPY

This study confirms that inflammation plays a role both in the initiation and maintenance of epilepsy. Inflammatory mediators may arise from tissues or circulating blood cells, involving both innate and adaptive immunity. The authors discuss potential therapeutic strategies targeting these inflammatory pathways.

Miller JW. Inflammation as a Target for Epilepsy Therapy: The Case of Natalizumab. Neurology. 2021 Nov 2;97(18):845-846. doi: 10.1212/WNL.0000000000012768. Epub 2021 Sep 14. PMID: 34521688.

THE ROLE OF INFLAMMATION IN THE DEVELOPMENT OF EPILEPSY

This review focuses on how inflammation contributes to epileptogenesis and suggests that treating inflammation may be a key factor in epilepsy management.

Rana, A., Musto, A.E. The role of inflammation in the development of epilepsy. J Neuroinflammation 15, 144 (2018). https://doi.org/10.1186/s12974-018-1192-7

FEBRILE INFECTION-RELATED EPILEPSY SYNDROME (FIRES)

This article examines FIRES—a rare but severe form of epilepsy that arises after a febrile illness. The syndrome is characterized by refractory status epilepticus and is linked to inflammatory processes. Anti-inflammatory treatments, including ketogenic diet and drugs such as anakinra or tocilizumab, have shown variable effectiveness.

Epilepsy Foundation: https://www.epilepsy.com/what-is-epilepsy/syndromes/febrile-infection-related-epilepsy-syndrome?utm_source=chatgpt.com

VIRUS-INDUCED EPILEPSY AND EPILEPSY IN PATIENTS WITH VIRAL INFECTIONS

This study reviews the bidirectional relationship between viral infections and epilepsy. It notes that while antiseizure medications remain the mainstay of treatment, antiviral therapy may be necessary in cases where seizures are associated with viral infections.

Costa B, Vale N. Virus-Induced Epilepsy vs. Epilepsy Patients Acquiring Viral Infection: Unravelling the Complex Relationship for Precision Treatment. Int J Mol Sci. 2024 Mar 27;25(7):3730. doi: 10.3390/ijms25073730. PMID: 38612542; PMCID: PMC11011490.

INFLAMMATION IN GENETIC EPILEPSY

This study indicates that neuroinflammation may serve as a mechanistic link between genetic and acquired epilepsy, suggesting that anti-inflammatory treatments could provide potential benefits for some forms of genetic epilepsy.

Vanderbilt University Medical Center: https://news.vumc.org/2021/01/21/inflammation-genetic-epilepsy/?utm_source=chatgpt.com

Conclusion
These studies emphasize the importance of considering both infectious and inflammatory processes in the pathogenesis and treatment of epilepsy. They also highlight the potential of anti-inflammatory and anti-infective therapies as adjunctive treatment strategies, particularly in cases where conventional antiepileptic drugs prove insufficient.

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