Epilepsy: here is everything you need to know about this disease

EPILEPSY - THE SIGNS AND SYMPTOMS, HOW A DIAGNOSIS IS MADE AND WHAT TREATMENT TO EXPECT

INTRODUCTION

Epilepsy is defined by the recurrence of unprovoked seizures. It is one of the most common chronic neurological disorders worldwide. It is characterized by a predisposition to recurrent, unprovoked seizures which occur due to abnormal, excessive, or synchronous electrical discharges in the brain. A single seizure does not necessarily constitute epilepsy. According to the International League Against Epilepsy (ILAE), epilepsy is diagnosed when a person has:

• At least two unprovoked seizures occurring more than 24 hours apart;
• One unprovoked seizure with a high (>60%) probability of further seizures over the next 10 years; or
• A diagnosis of an epilepsy syndrome.

Epilepsy is a major public health problem due to its impact on quality of life, education, employment, mental health, and mortality.

EPIDEMIOLOGY (spread of disease) and GLOBAL BURDEN

According to the World Health Organization:

• Approximately 50 million people worldwide live with epilepsy.
• Around 80% live in low- and middle-income countries.
• Nearly 5 million people are diagnosed annually.
• Up to 70% of patients can become seizure-free with appropriate treatment.

Epilepsy contributes substantially to disability-adjusted life years (DALYs), particularly in resource-limited settings.

THE SOUTH AFRICAN SITUATION

The estimated number of people suffering from epilepsy in South Africa is thought to be:

• 6–10 per 1,000 population
• Higher prevalence in may occur in rural communities
• Significant treatment gap in underserved areas is extremely common

Contributing factors include:

• HIV/AIDS
• Tuberculosis involving the central nervous system
• Neurocysticercosis (in endemic areas)
• Traumatic brain injury
• Perinatal complications
• Stroke

RISK FACTORS

In Children

• Birth asphyxia (delayed oxygen to the baby during birth)
• Congenital brain abnormalities
• Genetic syndromes
• Neonatal infections
• Metabolic disorders

With Adults

• Traumatic brain injury
• Stroke
• Brain tumours
• HIV-associated neurological disease
• Alcohol withdrawal
• Central nervous system infections

In the Elderly

• Stroke
• Dementia
• Brain tumours
• Neurodegenerative diseases

PATHOPHYSIOLOGY - WHY DO SEIZURES THEN OCCUR?

Epileptic seizures occur due to:

• Excessive neuronal excitation
• Reduced inhibitory neurotransmission (particularly involving GABA)
• Increased excitatory neurotransmission (especially glutamate)
• Abnormal ion channel function
• Structural brain lesions

At the level of the brain, the balance between neuronal excitation and inhibition becomes disrupted, leading to hypersynchronous (severe, irregular firing) of electrical activity.

In addition, researchers has identified possible genetic traits that may lead to epilepsies which may create excessive gene suppression and/or overexpression. Healthcare specialists has expressed that the genetic-related epilepsies require precise dosing to avoid any unfortunate side effects. It has been identified that future clinical trials must focus and prioritize rigorous evaluation to establish long-term safety, efficacy, and impact on cognitive and neurodevelopmental trajectories.

CLASSIFICATION OF SEIZURES

Epileptic Seizures are Classified into Two Specific Categories - they are:

1. FOCAL ONSET SEIZURES AND (2.) GENERAL-ONSET SEIZURES

1. FOCAL-ONSET SEIZURES

These originate from one hemisphere, focal awareness is perceived by the patient. The patient often remains conscious.

Examples include:

• Sensory symptoms
• Visual disturbances
• Motor twitching
• Autonomic symptoms

Focal Impaired Awareness Seizures can also occur within this category.

With this type of seizures, the patient has impaired consciousness. Common features includes:

• Staring
• Lip smacking
• Hand rubbing
• Confusion after seizure

(2.) GENERALIZED-ONSET SEIZURES

The origin of the seizure begins simultaneously in both hemispheres. These types of seizures, are described Generalized-Tonic-Clonic. This is the most recognised type. Tonic Seizures causes sudden muscle stiffness, while clonic seizures results in rhythmic jerking With these seizures the risk of injury is high. Clinical stages includes:

• Loss of consciousness
• Tonic stiffening
• Clonic jerking
• Postictal confusion

Absence Seizures are also classified within this category and tend to be more common in children. Features may include:

• Brief staring spells
• Last 5–20 seconds
• No postictal confusion

There are also two other types of seizures, that falls within this category as well. One of these are called Myoclonic Seizures. The seizures consists of brief muscle jerks. The other type of seizure is called Atonic Seizures. This type of seizure includes sudden loss of muscle tone.

Within the Clinical Presentation of most Seizures some patients experience what’s called an aura. A aura is a strange sensation you get, that may be related to:

• Strange smell
• Déjà vu
• Rising abdominal sensation - sometimes framed as a feeling “in the pit of your stomach”
• Unreasonable Fear
• Weird Visual experiences

During the Seizure, possible manifestations include:

Motor

• Generalized convulsions
• Limb jerking
• Muscle stiffening

Non-Motor

• Altered awareness
• Blank stare
• Behavioural arrest
• Speech arrest

Autonomic

• Sweating
• Palpitations
• Salivation

After the Seizure (Postictal Phase), patients may develop:

• Confusion
• Sleepiness
• Headache
• Muscle pain
• Temporary weakness (Todd's paresis)

DIAGNOSIS

Key information needed in order to make a proper diagnosis, includes:

• Witness description
• Duration
• Recovery
• Triggers
• Family history
• Medication history
• Substance use.

During the consultation, the medical practitioner, may do a physical examination, may asses: the neurological functioning, ask about any previous trauma, infections or cardiovascular status.

The gold standard in diagnosing Epilepsy is in performing an Electroencephalogram (EEG). It detects abnormal epileptiform activity in the brain. However, a normal EEG does not exclude epilepsy. In these cases a CT scan or MRI may be needed to be performed.

If epilepsy is excluded, other conditions which should be considered, includes:

Syncope, Psychogenic non-epileptic seizures, Migraine, Transient ischaemic attack, Sleep disorders, Movement disorders, Hypoglycaemia.

CLINICAL MANAGEMENT

Clinical management typically centres on the administration of antiseizure medications, which successfully achieve seizure control in approximately 70% of the patient population. However, cases of drug-resistant epilepsy present a persistent therapeutic challenge, often requiring alternative interventions such as surgical procedures or specialized behavioural strategies to mitigate morbidity.

For patients failing traditional pharmacotherapy, neuromodulation techniques such as vagus nerve stimulation or dietary modifications like the ketogenic diet may offer improved outcomes.

For individuals whose seizures remain uncontrolled despite adhering to two appropriately chosen and tolerated antiseizure medication regimens, timely surgical evaluation is warranted. This proactive strategy is vital, as the accumulation of recurrent seizures is linked to progressive cognitive decline and elevated risks of mortality, notably sudden unexpected death in epilepsy.

Addressing these multifaceted challenges necessitates a shift from loosely informed empiricism toward a new paradigm of data-driven, patient-centered precision therapy. This evolution relies on the integration of multi-omics data with multicentre databases to refine genotype-phenotype-treatment correlations. Such a framework facilitates the development of non-invasive, multimodal monitoring techniques to assess treatment efficacy and track drug delivery, ensuring compliance throughout the lifespan of the patient. Furthermore, the adoption of interdisciplinary workflows involving neurologists, oncologists, and regulatory experts is imperative to streamline patient access to both repurposed and novel targeted interventions. In this context, the integration of deep phenotyping with molecular data is vital to bridge the gap between genetic models and the heterogeneous nature of human disease.

As a patient is having an Acute Seizure - First Aid should consist of the following things to do and not to do.

Do:

✓ Protect the patient from any injury

✓ Place patient on their side after seizure, with the knee on the ground, bent inward towards the patient’s body.

✓ Loosen tight clothing

✓ Time the seizure

Do NOT:

✗ Restrain

✗ Put objects into mouth

✗ Give food or drink during seizure

If the patient experiences on-going seizures, it is termed: Status Epilepticus, which is a medical emergency. During Status Epilepticus, the seizures lasts ≥5 minutes, or are recurrent without recovery of consciousness. Initial Management should incluse:

• Protecting the Airway, as well as their, Breathing, blood Circulation, Oxygen supply, and from a medical perspective: Blood glucose should be tested and well maintained, as well as ensuring intravenous (IV) access

Expect the First-Line Medication to be: A Benzodiazepine, such as: Lorazepam (IV, where available), Diazepam (IV or rectal) or Midazolam (IM, buccal, or intranasal in appropriate settings)

The Second-Line Medication may include the following options: Levetiracetam, Valproate, Fosphenytoin or Phenytoin.

If seizures persist (refractory status epilepticus), intensive care and continuous anaesthetic infusions may be required.

Long-Term Management

To avoid the recurrence of on-going seizures, the choice of Antiseizure Medications drug selection depends on:

• Seizure type
• Age
• Sex
• Pregnancy potential
• Comorbidities
• Drug interactions

Common medications include:

Medication

Common Uses: Levetiracetam, Lamotrigine, Valproate, Carbamazepine, Oxarbazepine

General principles include:

• Start with one medication (monotherapy) where possible.
• Increase the dose gradually to achieve seizure control while minimizing adverse effects.
• Consider combination therapy only if monotherapy is ineffective.

Non-Pharmacological Management

Lifestyle advice includes:

• Medication adherence
• Adequate sleep
• Avoid excessive alcohol
• Stress management
• Regular follow-up
• Avoid known seizure triggers

Selected patients with drug-resistant epilepsy may benefit from:

• Epilepsy surgery
• Vagus nerve stimulation
• Responsive neurostimulation (where available)
• Ketogenic diet (particularly in some children)

Complications of long-standing epilepsy and treatment of it, may include:

• Physical injury
• Burns
• Fractures
• Depression
• Anxiety
• Cognitive impairment
• Social stigma
• Employment challenges
• Sudden Unexpected Death in Epilepsy (SUDEP)

Prognosis

• Approximately 60–70% of patients achieve good seizure control with appropriate antiseizure medication.
• Drug-resistant epilepsy occurs in about 30% of patients.
• Early diagnosis, appropriate classification of seizure type, adherence to treatment, and regular follow-up improve outcomes.

Prevention

Primary prevention focuses on reducing avoidable causes:

• Improve antenatal and obstetric care
• Prevent traumatic brain injury (e.g., road safety, helmets)
• Control central nervous system infections
• Vaccination where appropriate
• Effective management of hypertension and stroke risk factors
• HIV prevention and treatment

Secondary prevention includes:

• Early diagnosis
• Prompt initiation of appropriate antiseizure medication
• Patient education to reduce seizure recurrence and complications

Conclusion

Epilepsy is a common, treatable neurological disorder with important clinical and public health implications. Most patients can achieve good seizure control when the condition is accurately diagnosed, appropriately classified, and managed using evidence-based pharmacological and non-pharmacological strategies. In South Africa and other low- and middle-income countries, strengthening access to diagnosis, affordable medicines, specialist services, and community education remains essential to reducing the treatment gap and improving the quality of life of people living with epilepsy.

References include, but not limited to:

A roadmap for precision medicine in the epilepsies. (2015). The Lancet Neurology, 14(12), 1219–1228. Elsevier BV. https://doi.org/10.1016/s1474-4422(15)00199-4

Abduraupova, M. (2026a). EPILEPSY IN ADULTS: ETIOLOGY, DIAGNOSIS, AND LONG-TERM MANAGEMENT. Zenodo (CERN European Organization for Nuclear Research). https://doi.org/10.5281/zenodo.18640869

Abduraupova, M. (2026b). EPILEPSY IN ADULTS: ETIOLOGY, DIAGNOSIS, AND LONG-TERM MANAGEMENT. Zenodo (CERN European Organization for Nuclear Research). https://doi.org/10.5281/zenodo.18640868

Armstrong, C., & Marsh, E. D. (2021). Electrophysiological Biomarkers in Genetic Epilepsies [Review of Electrophysiological Biomarkers in Genetic Epilepsies]. Neurotherapeutics, 18(3), 1458–1467. Springer Science+Business Media. https://doi.org/10.1007/s13311-021-01132-4

Balestrini, S., Mei, D., Sisodiya, S. M., & Guerrini, R. (2023). Steps to Improve Precision Medicine in Epilepsy. Molecular Diagnosis & Therapy, 27(6), 661–672. https://doi.org/10.1007/s40291-023-00676-9

Knowles, J. K., Helbig, I., Metcalf, C. S., Lubbers, L. S., Isom, L. L., Demarest, S., Goldberg, E. M., George, A. L., Lerche, H., Weckhuysen, S., Whittemore, V., Berkovic, S. F., & Lowenstein, D. H. (2022). Precision medicine for genetic epilepsy on the horizon: Recent advances, present challenges, and suggestions for continued progress [Review of Precision medicine for genetic epilepsy on the horizon: Recent advances, present challenges, and suggestions for continued progress]. Epilepsia, 63(10), 2461–2475. Wiley. https://doi.org/10.1111/epi.17332

Mastrangelo, M., Salpietro, V., & Sullivan, J. (2022). Editorial: Genetically determined epilepsies: Perspectives in the era of precision medicine. Frontiers in Neurology, 13. https://doi.org/10.3389/fneur.2022.1036846

Nguyen, L. H., & Bordey, A. (2021). Convergent and Divergent Mechanisms of Epileptogenesis in mTORopathies [Review of Convergent and Divergent Mechanisms of Epileptogenesis in mTORopathies]. Frontiers in Neuroanatomy, 15. Frontiers Media. https://doi.org/10.3389/fnana.2021.664695