Epilepsy Explained: Pathophysiology, Diagnosis, and Management

This presentation titled “Comprehensive Epilepsy Overview” is designed for Pharm.D Therapeutics III students, educators, and healthcare professionals seeking a complete understanding of epilepsy and its management.
It provides a detailed, evidence-based explanation of the etiology, classification, pathophysiology, clinical presentation, diagnosis, and pharmacological as well as non-pharmacological treatment of epilepsy.
Epilepsy is a chronic neurological disorder characterized by recurrent, unprovoked seizures caused by abnormal, excessive neuronal activity in the brain. This slide deck walks through the topic systematically — from the basic mechanisms of neuronal excitability to advanced therapeutic interventions, aligning with Pharm.D curriculum standards and clinical practice guidelines.
Contents Covered
• Introduction & Definition – Overview of epilepsy as a neurological disorder and its global burden.
• Epidemiology – Current prevalence data globally and in India, with age and gender distribution.
• Etiology / Causes – Genetic, structural, metabolic, infectious, immune, and idiopathic factors (ILAE 2017 classification).
• Pathophysiology – Stepwise mechanism from neuronal hyperexcitability, paroxysmal depolarization shifts, and propagation of abnormal discharges to epileptogenesis and chronic epilepsy.
• Types of Seizures – Focal, generalized, and unknown onset; clinical manifestations and EEG features.
• Clinical Presentation – Signs and symptoms based on seizure type; preictal, ictal, and postictal phases explained clearly.
• Diagnosis – Role of history, EEG, neuroimaging (MRI, CT), metabolic work-up, and therapeutic drug monitoring.
• Treatment Overview
o Goals and principles of therapy.
o Pharmacologic management with detailed classification of antiepileptic drugs (AEDs).
o Mechanism of action (Na⁺/Ca²⁺ channel blockade, GABA enhancement, glutamate inhibition).
o Adverse drug reactions and monitoring parameters.
o Non-pharmacologic measures: surgery, neurostimulation, ketogenic diet.
• First Aid & Emergency Care – Stepwise management during seizures; do’s and don’ts, and emergency referral points.
Educational Value
• Tailored for Pharm.D students (Therapeutics III), interns, and clinical pharmacists.
• Supports academic presentations, viva preparation, and community awareness programs.
• Follows WHO and ILAE guidelines for epilepsy management.
• Includes visuals, flowcharts, and first-aid protocols for better understanding.

1. EPILEPSY Prepared By, Dr. S. Satheesh, Pharm.D., Associate Professor, Dept of Pharmacy Practice, JKK Munirajah Institute of Health Sciences College of Pharmacy, T. N. Palayam, Gobi (Tk), Erode (Dt) - 638506

2. INTRODUCTION Definition of Epilepsy Epilepsy is a chronic neurological disorder characterized by recurrent, unprovoked seizures due to abnormal, excessive electrical discharges in neurons of the brain. A seizure is a sudden, transient episode of altered consciousness, behavior , sensation, or motor activity caused by paroxysmal neuronal activity . ILAE (International League Against Epilepsy) Definition Epilepsy is diagnosed when an individual has: Two or more unprovoked seizures occurring at least 24 hours apart , OR One unprovoked seizure with a ≥60% probability of recurrence over the next 10 years, OR Diagnosis of an epileptic syndrome (e.g., Lennox- Gastaut , Juvenile Myoclonic Epilepsy).

3. CLASSIFICATION Epilepsy classification is based on: Origin of seizure activity (which part of brain is affected) Clinical features (consciousness, motor, sensory involvement) EEG findings The International League Against Epilepsy (ILAE 2017) provides the current framework for classification. Partial Seizure Generalized Seizure Unknown Onset Seizures Epileptic Syndromes

4. I. Focal (Partial) Epilepsy C. Focal → Bilateral Tonic–Clonic Seizure begins in one area and spreads to involve both hemispheres. Patient loses consciousness and develops generalized convulsions . A. Focal Aware Seizures (Simple Partial) Consciousness not impaired . Manifestations depend on area involved: Motor: jerking of one limb (Jacksonian seizure) Sensory: tingling, visual/auditory hallucinations Autonomic: flushing, sweating Psychic: déjà vu, fear Seizures start in a specific region (focus) of one cerebral hemisphere. B. Focal Impaired Awareness Seizures (Complex Partial) Consciousness impaired during the event. Often originate from temporal lobe . Symptoms: Automatisms (lip smacking, fumbling) Staring spells Postictal confusion

5. II. Generalized Epilepsy Seizure activity involves both hemispheres from the onset. Consciousness is always impaired . A. Generalized Tonic–Clonic (Grand Mal) Most common type. Sudden loss of consciousness → tonic phase (rigidity) → clonic phase (jerking). Postictal confusion, headache, drowsiness. B. Absence (Petit Mal) Brief loss of awareness (5–20 sec). “Blank stare” → no fall → resumes activity unaware of event. EEG: 3-Hz spike-and-wave pattern. Common in children. C. Myoclonic Seizures Sudden, brief jerks of limbs or face. No loss of consciousness. Seen in juvenile myoclonic epilepsy. D. Atonic Seizures Sudden loss of muscle tone → falls (“drop attacks”). Usually in children with Lennox– Gastaut syndrome. E. Tonic or Clonic Only Only one phase present. Tonic = sustained muscle contraction. Clonic = repetitive jerking movements.

6. Other Epilepsy Types III. Unknown Onset Seizures Seizures where the origin is uncertain due to incomplete data. Common in patients found unconscious or unobserved during seizure onset. IV. Epileptic Syndromes Groups of symptoms that define distinct clinical entities : Juvenile Myoclonic Epilepsy (JME) Lennox– Gastaut Syndrome Infantile Spasms (West Syndrome) Temporal Lobe Epileps

7. EPIDEMIOLOGY Global: In 2021, there were approximately 51.7 million people (95% UI 44.9–58.9 million) with epilepsy worldwide. ( thelancet.com ) Systematic review (2017, Fiest et al.): The pooled lifetime prevalence of epilepsy was 7.60 per 1,000 persons (95% CI 6.17–9.38); the annual cumulative incidence was 67.77 per 100,000 persons (95% CI 56.69–81.03). ( PMC ) India: According to Amudhan V et al. (2015), India is home to nearly 12 million persons with epilepsy , contributing to about one-sixth of the global burden. ( PubMed ) India prevalence range: From meta-analysis of Indian studies (1964 to 2012) prevalence of epilepsy ranged 2.5 to 11.9 per 1,000 population . (Sridh­aran & Murthy 2012) ( Lippincott Journals ) Indian incidence example: A study from Kolkata (India) estimated an age-standardised incidence rate of 27.3 per 100,000 per year . ( Lippincott Journals )

8. ETIOLOGY (CAUSES) OF EPILEPSY Category Key Mechanism / Examples 1. Genetic (Idiopathic) Caused directly by known or presumed genetic defects → alter ion channels, neurotransmitter receptors, or synaptic function. Examples: SCN1A (Na⁺ channel) → Dravet syndrome; KCNQ2/3 → benign familial neonatal epilepsy; CACNA1A (Ca²⁺ channel) → absence seizures. 2. Structural (Symptomatic) Due to identifiable brain lesions or damage visible on imaging (MRI/CT). Examples: Stroke, traumatic brain injury, brain tumors, cortical dysplasia, hippocampal sclerosis, congenital malformations. 3. Metabolic Secondary to inborn or acquired errors in metabolism → altered neuronal energy or electrolyte balance. Examples: Hypoglycemia, hypocalcemia , hyponatremia, uremia , hepatic encephalopathy, mitochondrial disorders. 4. Infectious Direct CNS infection or post-infectious scarring → neuronal hyperexcitability. Examples: Neurocysticercosis, meningitis, encephalitis, malaria, tuberculosis, HIV, Japanese encephalitis. 5. Immune Autoantibodies attack neuronal antigens → disrupt synaptic signaling. Examples: Anti-NMDA receptor encephalitis, LGI1 antibody encephalitis, autoimmune limbic encephalitis. 6. Unknown (Cryptogenic) No clear cause despite evaluation. May involve subtle genetic or acquired mechanisms not yet identified. According to the ILAE 2017 classification recognizes six etiologic categories .

9. PATHOPHYSIOLOGY OF EPILEPSY

10. PATHOPHYSIOLOGY OF EPILEPSY 1. Normal Neuronal Activity Under normal conditions, the brain maintains a fine balance between excitation and inhibition. Excitatory signaling is mediated by glutamate , while inhibitory control is provided by GABA . Stable ionic gradients (Na⁺, K⁺, Ca²⁺, Cl⁻) and controlled neuronal firing ensure smooth and coordinated brain activity. This equilibrium prevents abnormal discharges and maintains healthy communication across neuronal circuits. 2. Trigger / Initial Insult A variety of external or internal insults can disturb this delicate excitatory–inhibitory balance. Head trauma, stroke, infections (such as meningitis or encephalitis), brain tumors, metabolic disturbances, or genetic mutations may initiate the process. These triggers cause disruption of normal synaptic regulation, leading to neuronal hyperexcitability in localized brain regions.

11. PATHOPHYSIOLOGY OF EPILEPSY 3. Neuronal Hyperexcitability When the balance tips toward excitation, neurons become hyperactive. This occurs due to increased glutamate release and reduced GABA-mediated inhibition , resulting in abnormal depolarization known as Paroxysmal Depolarization Shifts (PDS) . These prolonged depolarizations generate bursts of action potentials, causing clusters of neurons to fire excessively and in synchrony. 4. Propagation of Abnormal Discharges Once initiated, abnormal electrical activity spreads through neuronal networks. This propagation occurs via thalamocortical pathways , axonal collaterals , and inter-neuronal gap junctions . The recruitment of additional brain regions transforms local discharges into widespread events. If contained, the activity manifests as focal seizures ; if it spreads broadly, it leads to generalized seizures .

12. PATHOPHYSIOLOGY OF EPILEPSY 5. Epileptogenesis (Network Remodeling ) With repeated episodes or sustained injury, the brain undergoes structural and molecular remodeling . There is a loss of inhibitory interneurons and sprouting of excitatory mossy fibers , particularly in the hippocampus. Astrocyte and blood–brain barrier (BBB) dysfunction promote inflammation through cytokines such as IL-1 β and TNF- α , while microglial activation further enhances excitability. These changes create a self-reinforcing epileptogenic network capable of generating spontaneous discharges. 6. Kindling and Molecular Reprogramming Over time, repeated sub-threshold stimulation results in the kindling phenomenon , where excitatory pathways strengthen progressively and the seizure threshold diminishes. Activation of intracellular pathways such as mTOR and BDNF supports persistent excitatory circuit formation and synaptic reorganization. The brain effectively “reprograms” itself into a hyperexcitable state, maintaining the cycle of seizure generation.

13. PATHOPHYSIOLOGY OF EPILEPSY 7. Chronic Epilepsy Eventually, the brain reaches a state of self-perpetuating hyperexcitability , where seizures occur spontaneously and recurrently without external triggers. This represents chronic or clinical epilepsy . At this stage, persistent molecular and network changes—such as lowered seizure threshold, altered receptor expression, and gliosis—sustain ongoing abnormal discharges. The condition becomes a long-term neurological disorder characterized by recurrent, unprovoked seizures.

14. CLINICAL PRESENTATION / SIGNS AND SYMPTOMS OF EPILEPSY Seizure Type Clinical Features / Signs Focal Aware Seizure (Simple Partial) • Localized motor jerks (face, hand, one limb). • Sensory symptoms – tingling, numbness, visual flashes, sounds, odors . • Psychic aura – fear, déjà vu, jamais vu. • Autonomic changes – sweating, flushing, nausea, tachycardia. Focal Impaired Awareness Seizure (Complex Partial) • Altered awareness or responsiveness. • Staring spells, blank look. • Automatisms – lip smacking, chewing, picking at clothes. • Sudden behavioral arrest. • Possible progression to generalized tonic– clonic seizure. Focal to Bilateral Tonic–Clonic Seizure • Begins as focal (simple or complex). • Then spreads to both hemispheres → tonic– clonic movements. • Fall, cry, cyanosis, tongue bite, frothing, incontinence.

15. CLINICAL PRESENTATION / SIGNS AND SYMPTOMS OF EPILEPSY Seizure Type Clinical Features / Signs Generalized Tonic–Clonic (Grand Mal) • Sudden loss of consciousness. • Tonic phase: body stiffens, apnea , cyanosis. • Clonic phase: rhythmic jerking of limbs. • Cry, frothing, tongue bite, urinary incontinence. Absence Seizure (Petit Mal) • Brief (5–20 sec) lapse of awareness. • “Blank stare,” fluttering eyelids. • May pause mid-sentence and resume normally. • No fall, no warning. Myoclonic Seizure • Sudden, brief, shock-like jerks (arms, shoulders, face). • Often in early morning after waking. • No warning or loss of posture. Atonic Seizure (“Drop Attack”) • Sudden loss of muscle tone → fall. • Head may drop forward. • Brief (seconds), immediate recovery.

16. CLINICAL PRESENTATION / SIGNS AND SYMPTOMS OF EPILEPSY Seizure Type Clinical Features / Signs Tonic Seizure • Sustained muscle contraction (few seconds). • Body stiffens, may fall backward. • Eyes open, face may grimace. Clonic Seizure • Repetitive, rhythmic jerking of limbs. • Without tonic phase. Non-Motor (Atypical Absence / Cognitive / Emotional) • Slow onset and termination. • Changes in emotion, thinking, or behavior . • Often associated with developmental epileptic syndromes.

17. DIAGNOSIS OF EPILEPSY Detailed History & Witness Account Most important diagnostic step. Describes onset, aura, body movements, duration, and recovery (postictal phase). Electroencephalogram (EEG) Detects abnormal cortical discharges. Findings: spike-and-wave or sharp-wave patterns. 3 Hz spike-and-wave → Absence seizure . Neuroimaging (MRI / CT Brain) Identifies structural causes such as tumors, stroke, trauma, cortical dysplasia, or hippocampal sclerosis.

18. DIAGNOSIS OF EPILEPSY Blood & Metabolic Tests Rule out metabolic causes (e.g., hypoglycemia, electrolyte imbalance, uremia , hepatic failure). Video EEG / Long-term Monitoring Confirms diagnosis and differentiates from psychogenic non-epileptic seizures (PNES). Genetic / CSF / Specialized Tests (If indicated) Used in pediatric , familial, or infection-related epilepsy cases.

19. TREATMENT Goals of Therapy Achieve complete seizure control with minimal adverse effects . Improve quality of life and ensure normal social functioning . Prevent status epilepticus and long-term complications. General Principles Start anti-epileptic drug (AED) only after confirmed diagnosis of epilepsy (≥2 unprovoked seizures). Begin with monotherapy → titrate gradually to optimal dose. If ineffective → switch or use combination therapy . Avoid abrupt drug withdrawal (risk of rebound seizures). Choose drug based on seizure type , age , comorbidity , and safety profile .

20. TREATMENT Non-Pharmacologic Measures Adequate sleep, stress reduction, avoid alcohol. Identify and avoid seizure triggers (flashing lights, sleep deprivation). Educate patient & family on medication adherence. Safety precautions (avoid swimming alone, driving restrictions).

21. PHARMACOLOGIAL THERAPY Pharmacological Class Examples of Drugs Barbiturates Phenobarbital Deoxybarbiturate Primidone Hydantoin Derivatives Phenytoin, Fosphenytoin Iminostilbene Derivatives Carbamazepine, Oxcarbazepine Succinimides Ethosuximide Aliphatic Carboxylic Acids Valproic acid (Sodium valproate), Divalproex sodium Benzodiazepines Clonazepam, Diazepam, Lorazepam, Clobazam Phenyltriazine Derivative Lamotrigine Cyclic GABA Analogues Gabapentin, Pregabalin Newer / Miscellaneous Drugs Topiramate, Zonisamide, Levetiracetam, Vigabatrin, Tiagabine, Lacosamide, Felbamate, Rufinamide

22. PHARMACOLOGIAL THERAPY Barbiturates (e.g., Phenobarbital) Class: Barbiturate derivative. MOA: Enhances GABA-mediated chloride influx by prolonging the duration of GABA_A receptor channel opening , causing neuronal hyperpolarization and decreased excitability. ADR: Sedation, tolerance, cognitive impairment, dependence, megaloblastic anemia (rare), respiratory depression (in overdose). Deoxybarbiturate (e.g., Primidone) Class: Prodrug converted to phenobarbital and phenylethylmalonamide (PEMA). MOA: Same as barbiturates — potentiates GABAergic inhibition and reduces neuronal firing. ADR: Sedation, ataxia, nystagmus, behavioral disturbances in children.

23. PHARMACOLOGIAL THERAPY Hydantoin Derivatives (e.g., Phenytoin, Fosphenytoin ) Class: Sodium channel blocker. MOA: Stabilizes neuronal membranes by prolonging Na⁺ channel inactivation , preventing repetitive firing. ADR: Gingival hyperplasia, hirsutism, ataxia, nystagmus, megaloblastic anemia, teratogenicity ( fetal hydantoin syndrome ). Iminostilbenes (e.g., Carbamazepine, Oxcarbazepine) Class: Tricyclic anticonvulsant. MOA: Blocks voltage-gated Na⁺ channels → inhibits high-frequency firing. ADR: Diplopia, ataxia, dizziness, hyponatremia (SIADH), leukopenia, rash (SJS/TEN).

24. PHARMACOLOGIAL THERAPY Succinimides (e.g., Ethosuximide) Class: Succinimide derivative. MOA: Inhibits T-type Ca²⁺ channels in thalamic neurons → suppresses rhythmic discharges causing absence seizures. ADR: Nausea, vomiting, drowsiness, headache, blood dyscrasias (rare). Aliphatic Carboxylic Acids (e.g., Valproic Acid, Divalproex) Class: Broad-spectrum antiepileptic. MOA: Multiple actions – blocks Na⁺ and T-type Ca²⁺ channels and enhances GABA synthesis. ADR: Hepatotoxicity, pancreatitis, weight gain, tremor, teratogenicity ( neural tube defects ).

25. PHARMACOLOGIAL THERAPY Benzodiazepines (e.g., Diazepam, Clonazepam, Lorazepam, Clobazam) Class: Benzodiazepine derivatives. MOA: Enhance GABA_A receptor activity → increase frequency of chloride channel opening → neuronal inhibition. ADR: Sedation, tolerance, dependence, withdrawal seizures, respiratory depression (IV). Phenyltriazine Derivative (e.g., Lamotrigine) Class: Phenyltriazine antiepileptic. MOA: Blocks Na⁺ channels and inhibits glutamate release . ADR: Rash, Stevens–Johnson syndrome, dizziness, diplopia, insomnia.

26. PHARMACOLOGIAL THERAPY Cyclic GABA Analogues (e.g., Gabapentin, Pregabalin) Class: GABA analogs (though they do not act on GABA receptors). MOA: Bind to α2δ subunit of voltage-gated Ca²⁺ channels , reducing excitatory neurotransmitter release. ADR: Drowsiness, dizziness, weight gain, peripheral edema .

27. PHARMACOLOGIAL THERAPY Newer Agents (e.g., Levetiracetam, Topiramate, Zonisamide, Vigabatrin, Tiagabine, Lacosamide) Levetiracetam: Modulates SV2A protein → ↓ neurotransmitter release. Topiramate / Zonisamide: Block Na⁺ channels + enhance GABA + inhibit glutamate receptors. Vigabatrin: Irreversible GABA transaminase inhibitor . Tiagabine: Inhibits GABA reuptake . Lacosamide: Enhances slow inactivation of Na⁺ channels. ADR: Somnolence, behavioral changes, visual field defects (Vigabatrin), cognitive slowing (Topiramate).

28. MONITORING PARAMETERS FOR ANTIEPILEPTIC DRUGS (AEDS) Clinical Monitoring Seizure frequency and severity: Record in a seizure diary to assess treatment effectiveness. Adherence to therapy: Evaluate patient compliance, missed doses, and timing of medication intake. Neurological status: Watch for sedation, ataxia, diplopia, tremor, and cognitive slowing. Behavioral changes: Irritability, mood swings, or depression (notably with Levetiracetam, Topiramate). Weight changes: Weight gain (Valproate, Gabapentin) or weight loss (Topiramate).

29. MONITORING PARAMETERS FOR ANTIEPILEPTIC DRUGS (AEDS) Therapeutic Drug Monitoring (TDM) Used for AEDs with a narrow therapeutic index or significant inter-patient variability. Drug Therapeutic Range (µg/mL) Toxic Level / Comments Phenytoin 10–20 Toxic > 30; monitor free phenytoin if low albumin. Carbamazepine 4–12 Toxic > 15; induces own metabolism (autoinduction). Valproic Acid 50–100 Toxic > 150; monitor liver enzymes & ammonia. Phenobarbital 15–40 Toxic > 50; monitor sedation, dependence. Lamotrigine, Levetiracetam 3–15 (variable) Clinical response preferred over routine levels. TDM samples should be drawn at steady state (usually after 5–7 half-lives).

30. MONITORING PARAMETERS FOR ANTIEPILEPTIC DRUGS (AEDS) Laboratory Monitoring Parameter Drugs to Monitor Reason / Concern Liver function tests (AST, ALT, bilirubin) Valproate, Carbamazepine, Phenytoin Hepatotoxicity. CBC (WBC, platelets) Carbamazepine, Valproate, Ethosuximide Risk of leukopenia, thrombocytopenia. Serum Sodium Carbamazepine, Oxcarbazepine Hyponatremia (SIADH). Renal function (BUN, creatinine) Gabapentin, Pregabalin, Levetiracetam Renal clearance adjustment. Ammonia levels Valproate Hyperammonemia → encephalopathy. Bone density / Vitamin D Long-term Phenytoin, Phenobarbital Osteopenia risk due to enzyme induction.

31. MONITORING PARAMETERS FOR ANTIEPILEPTIC DRUGS (AEDS) Special Monitoring Considerations Pregnancy: Valproate contraindicated — risk of neural tube defects. Use folic acid supplementation. Children: Growth, cognitive function, and behavioral patterns. Elderly: Sedation, falls, and drug–drug interactions (due to polypharmacy). Drug interactions: Enzyme inducers (Phenytoin, Carbamazepine, Phenobarbital) lower levels of other drugs.

32. FIRST AID FOR EPILEPSY Immediate First Aid Steps Stay calm and note the time and duration of the seizure. Protect the patient from injury: Clear the surrounding area of hard or sharp objects. Loosen tight clothing around the neck. Position: If possible, turn the patient gently onto their side (recovery position) to help saliva drain and prevent aspiration. Support the head: Place something soft (like folded clothing) under the head to prevent head injury. Do not restrain movements: Allow convulsions to happen naturally. Forcing restraint can cause fractures or muscle tears. After seizure stops: Check breathing and pulse. Keep the patient in lateral position and allow rest. Monitor for postictal confusion and reassure calmly.

33. DO’S DURING A SEIZURE Stay with the person until full recovery. Remove nearby objects that could cause harm. Loosen collar or tie to ease breathing. Place in recovery position after convulsions stop. Record seizure duration and features (important for diagnosis). If seizure lasts >5 minutes or repeats without recovery → call emergency help (risk of status epilepticus ). If diabetic, pregnant, or injured → seek medical assistance immediately.

34. DON’TS DURING A SEIZURE Do NOT put anything in the mouth (no spoons, fingers, water, or food) risk of choking or dental injury. Do NOT try to restrain the patient’s limbs during convulsion. Do NOT attempt mouth-to-mouth breathing during active seizure. Do NOT give medicines or fluids orally until the patient is fully conscious. Do NOT panic or crowd the patient ensure a calm and safe environment. Do NOT leave the patient alone immediately after the episode.

35. CALL FOR EMERGENCY HELP Seizure lasts longer than 5 minutes . Repeated seizures occur without regaining consciousness . First-ever seizure in a patient. Injury, head trauma, or breathing difficulty occurs. Patient is pregnant, diabetic, or has fever/infection .

36. Thank You!!!