After reading this note you will be able to describe the clinical approach to a patient with epilepsy or status epilepticus, list the common local aetiologies, interpret the key investigations and outline immediate and definitive management – remembering to verify drug doses and local protocols against the Kenya MoH guideline and your hospital formulary.
Definition
Epilepsy – a disorder characterised by ≥2 unprovoked seizures occurring >24 h apart, or one unprovoked seizure with a high risk of recurrence (≥60 % in the next 10 years).
Status epilepticus (SE) – a seizure lasting ≥5 min or recurrent seizures without full recovery of consciousness between episodes. It is a medical emergency because neuronal injury and systemic complications increase rapidly after the first few minutes.
Anatomy and physiology you need
| Structure | Relevance to seizures |
|---|---|
| Cerebral cortex | Site of synchronous neuronal firing that produces clinical seizures |
| Thalamocortical circuits | Modulate spread of ictal activity; important in generalized seizures |
| Hippocampus & limbic system | Common focus for temporal lobe epilepsy |
| Basal ganglia | Inhibitory influence; dysfunction can facilitate motor seizures |
| GABAergic interneurons | Primary inhibitory neurotransmission; loss → hyperexcitability |
| Glutamatergic neurons | Main excitatory drive; excess release promotes ictogenesis |
| Blood‑brain barrier | Disruption allows inflammatory mediators to lower seizure threshold |
Causes and risk factors (Kenyan context)
| Category | Typical aetiologies in Kenya |
|---|---|
| Structural brain lesions | Post‑traumatic scar, stroke, cerebral malaria, tuberculoma, HIV‑associated neurocognitive disorder, neurocysticercosis |
| Metabolic / toxic | Hypoglycaemia, hyponatraemia, uremia, antiretroviral toxicity, antimalarial drug interactions |
| Infectious | HIV, cerebral malaria, tuberculous meningitis, bacterial meningitis, neurocysticercosis |
| Genetic / developmental | Congenital malformations, perinatal hypoxia‑ischemia, sickle‑cell vaso‑occlusive cerebral infarcts |
| Immune‑mediated | Autoimmune encephalitis (e.g., NMDA‑R), rheumatic fever with chorea |
| Unknown (idiopathic) | Often reflects genetic predisposition not yet identified |
Risk factors specific to our setting include poor malaria control, high HIV prevalence, limited neuro‑imaging, and delayed treatment of bacterial meningitis or TB.
Pathophysiology
- Trigger (infection, trauma, metabolic derangement) →
- Neuronal injury → loss of GABA‑ergic inhibition & ↑ glutamate release →
- Hyper‑excitability of cortical networks →
- Synchronous discharge of neuronal populations → clinical seizure →
- Failure of termination mechanisms (e.g., exhausted inhibitory interneurons) → prolonged seizure activity → status epilepticus.
In status epilepticus, prolonged depolarisation leads to intracellular calcium overload, excitotoxicity, oxidative stress and ultimately neuronal death if not aborted promptly.
Clinical features
History – key questions
| Domain | Questions | Rationale |
|---|---|---|
| Seizure description | “What was the person doing when it started? How long did it last? Was there a loss of awareness? Any tonic‑clonic movements, stiffening, rhythmic jerking, automatisms, tongue biting, incontinence?” | Determines type (focal vs generalized), duration (helps identify status), and whether the event was a true epileptic seizure or a mimic. |
| Pre‑ictal and post‑ictal state | “Did they feel an aura, headache, visual changes, or a sense of déjà vu before the event? How long did confusion, fatigue or headache last afterwards?” | Aura suggests focal onset; post‑ictal confusion is typical of generalized tonic‑clonic seizures and helps differentiate from psychogenic events. |
| Triggers / precipitants | “Recent fever, head injury, missed antiepileptic drugs, alcohol binge, sleep deprivation, menstrual cycle, new medication, substance use?” | Identifies reversible precipitants that may need urgent correction. |
| Past medical & family history | “Previous seizures, known CNS infection (TB meningitis, cerebral malaria), stroke, head trauma, HIV status, rheumatic fever, sickle‑cell disease, neuro‑developmental disorder?” | Many local etiologies (HIV, TB, malaria, sickle‑cell) predispose to epilepsy; family history points to genetic epilepsy. |
| Medication & adherence | “Current drugs (including antiretrovirals, anti‑TB, antimalarials), recent changes, missed doses?” | Non‑adherence is a common cause of breakthrough seizures and status. |
| Social & environmental factors | “Alcohol use, recreational drugs, exposure to pesticides, occupational hazards, access to care?” | Substance‑related seizures are frequent in young adults. |
| Pregnancy & obstetric history (women) | “Current pregnancy, complications, pre‑eclampsia, eclampsia?” | Eclampsia is a cause of status in pregnancy. |
| Frequency & pattern | “How many episodes, interval between them, any clustering?” | Helps classify epilepsy syndrome and assess control. |
| Safety & impact | “Driving, work, school performance, injuries, stigma?” | Guides counseling and need for protective measures. |
Examination – what to look for and why
| Finding | Why it matters |
|---|---|
| General appearance & level of consciousness | Post‑ictal drowsiness, ongoing seizure activity, or a non‑convulsive status may be evident. |
| Vital signs (BP, pulse, temperature, O₂ sat) | Fever may point to infection; hypotension or hypoxia suggests complications; hypertension may be seen in eclampsia. |
| Neurological exam – focal deficits | New weakness, cranial nerve palsy, visual field loss, or aphasia indicates a structural lesion (stroke, TB granuloma, malaria‑related infarct). |
| Post‑ictal tongue bite, bruises, bite marks | Supports a true convulsive seizure; lateral tongue bite is classic. |
| Skin examination – rash, petechiae | May hint at meningococcemia, severe malaria, or drug reaction. |
| Cardiovascular exam – murmurs, signs of endocarditis | Rheumatic fever can cause cerebral emboli leading to seizures. |
| Abdominal exam – splenomegaly, hepatomegaly | Suggests chronic malaria or sickle‑cell disease. |
| HIV‑related stigmata (oral thrush, lymphadenopathy) | Raises suspicion for opportunistic CNS infections. |
| Obstetric exam (if pregnant) – uterine height, edema | Helps identify eclampsia or pre‑eclampsia. |
| Mental status & cognition | Persistent confusion may indicate non‑convulsive status or post‑ictal encephalopathy. |
Differential diagnosis
| Condition | Points toward it | Distinguishing feature |
|---|---|---|
| Epileptic seizure (primary) | Typical motor activity, aura, post‑ictal confusion, EEG spikes | EEG shows epileptiform discharges; no metabolic derangement |
| Syncope with convulsive movements | Pre‑syncopal prodrome, brief loss of consciousness, rapid recovery | No post‑ictal confusion; normal EEG; cardiac cause on ECG |
| Psychogenic non‑epileptic attack (PNES) | Variable semiology, often triggered by stress, prolonged duration, resistance to antiepileptics | Normal EEG during event; lack of typical post‑ictal sleepiness |
| Febrile seizure (children) | Fever, age <5 y, brief generalized tonic‑clonic activity | Fever present; resolves quickly; no prior epilepsy |
| Metabolic encephalopathy (hypoglycaemia, hyponatraemia) | Altered mental state, precipitating illness, lab abnormalities | Correctable metabolic derangement; EEG shows diffuse slowing |
| CNS infection (TB meningitis, cerebral malaria) | Fever, neck stiffness, focal deficits, endemic exposure | CSF abnormalities, malaria smear, imaging showing lesions |
| Stroke / intracerebral haemorrhage | Sudden focal deficit, risk factors (hypertension, HIV vasculitis) | CT/MRI shows acute infarct or bleed |
| Eclampsia | Pregnancy >20 wks, hypertension, proteinuria, seizures | Resolves with magnesium sulfate; obstetric signs |
| Drug‑induced seizure (e.g., withdrawal, antiretroviral neurotoxicity) | Recent drug change, substance use, HIV therapy | Temporal relation to drug exposure; resolves on withdrawal |
Investigations
| Test | What it answers | Interpretation |
|---|---|---|
| Bedside glucose | Rule out hypoglycaemia as trigger | <2.8 mmol/L → treat, normal → look elsewhere |
| Full blood count & electrolytes | Detect infection, anaemia, electrolyte imbalance | Leukocytosis → infection; Na < 130 mmol/L → hyponatraemia seizure risk |
| Renal & liver function | Assess organ safety for antiepileptic drugs | Elevated transaminases → avoid hepatotoxic agents |
| HIV test (4th generation) | Identify HIV as underlying cause | Positive → consider opportunistic CNS infection |
| Malaria rapid diagnostic test / thick smear | Detect Plasmodium infection | Positive → treat malaria, may explain seizures |
| CSF analysis (if meningitis/encephalitis suspected) | Look for TB, bacterial, viral infection | Lymphocytic pleocytosis + low glucose → TB meningitis |
| Brain imaging (CT non‑contrast; MRI if available) | Identify structural lesions, bleed, infarct | Hyperdense lesion → haemorrhage; ring‑enhancing lesion → TB granuloma |
| Electroencephalogram (EEG) | Confirm epileptiform activity, classify seizure type | Interictal spikes → epilepsy; diffuse slowing → metabolic encephalopathy |
| Pregnancy test (women of reproductive age) | Exclude eclampsia | Positive → obstetric assessment |
| Serum antiretroviral levels (if on therapy) | Check for drug interactions or toxicity | Sub‑therapeutic → risk of seizures |
Diagnosis and severity
Diagnostic criteria (adapted from international consensus, applied locally)
- At least two unprovoked seizures >24 h apart or one unprovoked seizure with a high probability of recurrence (e.g., abnormal EEG, structural lesion).
- Exclusion of acute symptomatic causes (e.g., metabolic derangement, acute infection) by appropriate investigations.
- Classification into focal, generalized, or unknown onset based on history, exam, EEG, and imaging.
Severity grading for status epilepticus (used to guide urgency of treatment)
| Grade | Duration / clinical picture | Immediate action |
|---|---|---|
| Convulsive status | Continuous tonic‑clonic activity ≥5 min or recurrent seizures without full recovery | Immediate airway protection, IV benzodiazepine, rapid control of seizures. |
| Non‑convulsive status | Altered mental state with EEG seizure activity, no obvious motor signs | Urgent EEG, treat as status with IV benzodiazepine and load antiepileptic. |
| Refractory status | Seizure persists after first‑line benzodiazepine and a second‑line antiepileptic | Escalate to continuous infusions, consider ICU admission, treat underlying cause. |
| Super‑refractory | Status continues >24 h despite anesthetic agents | Multidisciplinary management, address complications (infection, organ failure). |
Severity of chronic epilepsy (for long‑term planning)
- Well‑controlled: No seizures for ≥12 months, adherent to therapy, normal EEG.
- Partially controlled: ≤2 seizures per year, occasional breakthrough, EEG shows interictal spikes.
- Uncontrolled: >2 seizures per year, frequent breakthrough, EEG with frequent discharges, or status episodes.
Severity assessment informs choice of antiepileptic class, need for specialist referral, and counseling on safety (driving, occupation, pregnancy).
Management
Immediate stabilisation
- Airway, Breathing, Circulation – place the patient in lateral recovery position; protect the airway; give supplemental O₂ if SpO₂ < 94 %.
- Terminate the seizure – give a rapid‑acting benzodiazepine (IV lorazepam or IM midazolam) as first‑line. If IV access is unavailable, use intranasal or buccal midazolam.
- Treat the underlying trigger – check glucose (treat hypoglycaemia), correct electrolyte disturbances, give antipyretics for fever, start anti‑TB therapy if TB meningitis is suspected, treat malaria promptly, and start ART/PCP prophylaxis in known HIV‑positive patients.
Definitive treatment
| Situation | Preferred drug class | Typical agents (no doses) | Rationale |
|---|---|---|---|
| Established epilepsy (after seizure control) | Sodium‑channel blockers | Phenytoin, carbamazepine, lamotrigine | Good for focal onset seizures; inexpensive and widely available. |
| Generalised tonic‑clonic seizures | Broad‑spectrum AEDs | Valproate, levetiracetam, phenobarbital | Effective for both focal and generalized seizures; valproate also covers absence. |
| Women of child‑bearing age | Avoid teratogenic AEDs | Levetiracetam, lamotrigine | Lower fetal risk. |
| HIV/TB co‑infection | Consider drug interactions | Adjust doses of enzyme‑inducing AEDs; prefer levetiracetam or valproate if possible | Minimise interaction with rifampicin and ART. |
| Status epilepticus refractory to benzodiazepine | Second‑line IV AED | Phenytoin, fosphenytoin, valproate, levetiracetam | Rapid loading stops ongoing seizure. |
| Refractory status (≥ 30 min) | Anesthetic agents | Midazolam infusion, propofol, pentobarbital | Induce burst‑suppression on EEG; ICU monitoring required. |
Monitoring & safety
- Continuous pulse oximetry, cardiac monitoring, and frequent neurological checks (Glasgow Coma Scale, seizure activity).
- Serum electrolytes, glucose, liver and renal function every 12–24 h while on IV AEDs.
- Observe for respiratory depression after benzodiazepines; be ready to ventilate.
- Educate patient/caregivers on seizure triggers, medication adherence, and when to seek emergency care.
Contra‑indications / safety
- Avoid benzodiazepines in severe respiratory compromise without airway support.
- Phenobarbital is contraindicated in severe hepatic failure.
- Valproate should not be used in known mitochondrial disease or severe liver disease.
- Phenytoin requires caution in patients with cardiac conduction disease (avoid rapid infusion).
Complications and prognosis
- Acute: aspiration pneumonia, traumatic injuries, rhabdomyolysis, hypoxic brain injury, status epilepticus‑related mortality (higher in HIV/TB meningitis).
- Chronic: cognitive decline, psychosocial stigma, depression, medication‑related side‑effects (e.g., gingival hyperplasia with phenytoin, bone loss with enzyme‑inducing drugs).
- Prognosis:
- Good in isolated provoked seizures (e.g., malaria, acute febrile illness) once the trigger is treated.
- Variable in structural epilepsy; seizure freedom achievable in 60‑70 % with appropriate AEDs.
- Status epilepticus carries a mortality of 10‑20 % in resource‑limited settings; early benzodiazepine administration improves outcome.
High‑yield exam points
- Look‑alike conditions: syncope with convulsive movements, psychogenic non‑epileptic seizures, hypoglycaemia, meningitis, cerebral malaria.
- Commonest wrong first step: delaying benzodiazepine administration while waiting for investigations.
- Examiner’s bedside questions:
- “What is your first drug and route for a convulsive status in a child with no IV line?”
- “How does HIV change your choice of AED?”
- “Explain why you would avoid phenobarbital in a patient with liver disease.”
- “What safety measures do you implement after giving a benzodiazepine?”
Clinical case
Case: A 22‑year‑old male university student presents after a witnessed generalized tonic‑clonic seizure lasting 3 minutes. He is post‑ictal, confused, with a tongue bite on the left side. No fever, no recent travel. Past history: HIV diagnosed 2 years ago, on first‑line ART, CD4 ≈ 350 cells/µL. No prior seizures.
Key findings:
- Normal vital signs, SpO₂ 98 % on room air.
- Blood glucose 5.2 mmol/L.
- No focal neurological deficit.
Questions
- What is the immediate next step?
Answer: Administer a rapid‑acting benzodiazepine (e.g., intranasal midazolam) to ensure seizure termination and protect the airway.
- Which antiepileptic drug class is preferred for long‑term therapy in this patient?
Answer: A broad‑spectrum AED with minimal interaction with ART, such as levetiracetam, is preferred.
- What investigations are essential before starting chronic therapy?
Answer: Baseline CBC, liver and renal function tests, serum electrolytes, and a non‑contrast head CT (to exclude structural lesion).
Practice questions
Question 1
A 6‑year‑old child is having a generalized tonic‑clonic seizure that has lasted 4 minutes. No IV line is available. What is the most appropriate next step?
A. Give oral phenobarbital
B. Give intranasal midazolam
C. Wait for the seizure to stop spontaneously
D. Start a high‑dose IV phenytoin
Answer: B. Give intranasal midazolam – rapid, non‑invasive benzodiazepine delivery for status in a child without IV access.
Question 2
A 35‑year‑old woman with known epilepsy presents with a focal seizure that progressed to a generalized tonic‑clonic seizure lasting 2 minutes. She is on carbamazepine and reports poor adherence. Which drug would you add to achieve better control without increasing hepatic enzyme induction?
A. Phenytoin
B. Phenobarbital
C. Valproate
D. Levetiracetam
Answer: D. Levetiracetam – broad‑spectrum, no enzyme induction, useful as add‑on therapy.
Question 3
A patient with cerebral malaria develops a seizure. Which of the following is the most appropriate acute management?
A. Immediate IV phenobarbital
B. Oral carbamazepine
C. IV benzodiazepine followed by IV levetiracetam if seizure persists
D. Wait for malaria treatment to take effect
Answer: C. IV benzodiazepine followed by IV levetiracetam if seizure persists – rapid seizure control, then a non‑interacting AED.
Question 4
Which of the following is a contraindication to using valproate in a patient with epilepsy?
A. Focal seizures
B. Pregnancy
C. HIV infection
D. History of status epilepticus
Answer: B. Pregnancy – valproate is teratogenic and should be avoided in women of child‑bearing potential.
Question 5
A 45‑year‑old man with TB meningitis is in non‑convulsive status epilepticus on EEG. He is already receiving rifampicin. Which AED is least likely to have a pharmacokinetic interaction with his anti‑TB regimen?
A. Phenytoin
B. Carbamazepine
C. Phenobarbital
D. Levetiracetam
Answer: D. Levetiracetam – minimal hepatic metabolism, therefore little interaction with rifampicin.
Drafted with AI assistance from standard references and reviewed for structure. Check details against your lecture notes and the Kenya MoH guideline.