Seizures

A seizure is a transient episode of signs or symptoms caused by abnormal, excessive or synchronous neuronal activity. Most seizures stop within 2 minutes.

Clinical relevance. A seizure lasting 5 minutes or more, or repeated seizures without recovery between them, is status epilepticus and needs drug treatment at once. After a first unprovoked seizure the recurrence risk is about 40 to 50 percent within 2 years.

Definitions. Epilepsy is diagnosed after two unprovoked seizures more than 24 hours apart, after one unprovoked seizure when the recurrence risk is at least 60 percent over 10 years, or when an epilepsy syndrome is recognised. A provoked seizure follows an acute systemic or brain insult and does not by itself mean epilepsy.

Mechanisms. Excess excitation or failure of inhibition in cortical networks, from structural injury, genetic channelopathy, metabolic derangement, toxins, drug withdrawal or infection.

Classification. Focal onset (aware or impaired awareness, motor or non-motor onset, with or without progression to bilateral tonic clonic), generalised onset (tonic clonic, absence, myoclonic, atonic, tonic) and unknown onset.

Temporal patterns. Single seizure, cluster (several in 24 hours with recovery between them) and prolonged seizure. The post-ictal state usually settles within an hour.

Key distinctions. Convulsive movements, incontinence and brief jerking are not specific. Onset, duration, lateral tongue biting and speed of recovery separate seizures from their mimics.

History from the patient and an eyewitness. Circumstances and posture at onset, prodrome, aura (rising epigastric sensation, deja vu, odour, focal sensory or motor symptoms), eye and head deviation, limb movements and their symmetry, cyanosis, duration, tongue biting, incontinence, injuries, and time to return to baseline. Confusion for more than 5 to 10 minutes after the event favours seizure. Ask about sleep deprivation, alcohol (quantity, last drink), drug use, missed antiseizure medicines, fever, headache, trauma and flashing lights.

Background. Previous seizures, febrile seizures, perinatal injury, head injury, stroke, CNS infection, brain tumour, neurocysticercosis exposure, HIV, cancer, family history of epilepsy, pregnancy, diabetes, renal and liver disease. Drugs that lower seizure threshold include tramadol, bupropion, theophylline, carbapenems, high dose penicillins, fluoroquinolones, isoniazid, clozapine, tricyclic antidepressants, ciclosporin and stimulants.

Examination. Airway, oxygen saturation, temperature, blood pressure, pulse, capillary glucose, Glasgow Coma Scale. Look for tongue laceration, injuries, focal deficit or post-ictal (Todd) paresis, neck stiffness, rash, fundal changes, neurocutaneous stigmata (adenoma sebaceum, cafe au lait macules, port wine stain), heart murmur or irregular rhythm, and lying and standing blood pressure.

Red flags

• Failure to return to baseline within 30 to 60 minutes
• Focal deficit, new headache, fever, neck stiffness or rash
• Head trauma, anticoagulation, cancer, HIV or immunosuppression
• Seizure clusters or recurrent seizures during the same illness
• First seizure after age 40 to 60
• Blood pressure of 140/90 mmHg or more in pregnancy over 20 weeks or the first 6 weeks postpartum
• Signs of alcohol or benzodiazepine withdrawal (tremor, sweating, tachycardia, hallucinations)
• Hypoglycaemia, hyponatraemia or other metabolic derangement on first tests
• Overdose or toxic exposure

Special groups. Pregnancy: eclampsia is the first consideration after 20 weeks. Older adults: structural causes (stroke, tumour, subdural haematoma) are more frequent, and non-convulsive status can present as unexplained confusion. Region specific: neurocysticercosis and cerebral malaria are leading causes in many tropical settings; every febrile seizure in a malaria endemic area needs a malaria test.

Provoked (acute symptomatic) seizure, metabolic and toxic

• Hypoglycaemia, non-ketotic hyperglycaemia
• Hyponatraemia, hypernatraemia, hypocalcaemia, hypomagnesaemia
• Uraemia, hepatic encephalopathy, hypoxia
• Alcohol withdrawal, benzodiazepine or barbiturate withdrawal
• Overdose or toxicity: tricyclic antidepressants, tramadol, bupropion, theophylline, isoniazid, cocaine, amphetamines, organophosphates, camphor, lithium
• Eclampsia

Provoked, infective and inflammatory

• Bacterial meningitis, viral encephalitis, brain abscess, subdural empyema
• Cerebral malaria
• Neurocysticercosis, tuberculoma, cerebral toxoplasmosis, cryptococcal meningitis, neurosyphilis, HIV related CNS disease
• Autoimmune encephalitis

Provoked, structural and vascular

• Ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, cerebral venous sinus thrombosis
• Acute head injury, subdural haematoma
• Hypertensive encephalopathy, posterior reversible encephalopathy syndrome
• Hypoxic brain injury after cardiac arrest

Unprovoked seizure and epilepsy

• Genetic generalised epilepsies (juvenile myoclonic epilepsy, childhood and juvenile absence epilepsy, generalised tonic clonic seizures alone)
• Structural focal epilepsy: post-stroke, post-traumatic, tumour, hippocampal sclerosis, cortical dysplasia, vascular malformation, post-infective scar
• Epilepsy of unknown cause

Mimics of seizure

• Convulsive syncope, cardiac arrhythmia
• Functional (psychogenic non-epileptic) seizures
• Transient ischaemic attack, migraine with aura
• Hypoglycaemia without seizure, narcolepsy with cataplexy, parasomnias, REM sleep behaviour disorder
• Movement disorders, panic attack with hyperventilation, transient global amnesia

Reasoning. Confirm the event, exclude and treat immediate causes, classify as provoked or unprovoked, then decide on investigation for epilepsy.

Bedside tests for everyone. Capillary glucose, oxygen saturation, temperature, blood pressure and a 12 lead ECG (QT interval, conduction disease and arrhythmia that may have caused a convulsive faint).

Blood tests. Glucose, sodium, potassium, calcium, magnesium, phosphate, urea, creatinine, liver function, full blood count, creatine kinase, and a pregnancy test in women of reproductive age.

Add venous blood gas with lactate (a raised lactate within 2 hours of a convulsion supports tonic clonic seizure, but the test cannot separate seizure from other causes of acidosis), malaria test where relevant, HIV test, toxicology screen and blood alcohol, and drug levels in treated epilepsy.

Serum prolactin has limited reliability and is not used to make the diagnosis.

Imaging. Emergency non-contrast CT head if there is failure to recover, focal deficit, head trauma, fever, anticoagulation, cancer, HIV or a first seizure at age over 40, with CT venography or angiography when thrombosis or vascular lesion is suspected. MRI brain with an epilepsy protocol within weeks for every adult with a first unprovoked seizure; MRI detects hippocampal sclerosis, dysplasia, small tumours and cavernomas that CT misses. In neurocysticercosis the CT shows ring enhancing or calcified lesions, and MRI shows the scolex and viable cysts.

EEG. Within 24 to 72 hours of a first seizure when epilepsy is suspected, with sleep deprivation or repeat recording if the first is normal. One routine EEG shows epileptiform discharges in about half of people with epilepsy, while discharges in people without epilepsy are uncommon. A normal EEG does not exclude epilepsy. Urgent EEG is needed when non-convulsive status is suspected in a patient who does not recover.

Lumbar puncture (after CT) for fever, meningism, immunosuppression or unexplained encephalopathy: opening pressure, cell count, protein, glucose with paired blood glucose, Gram stain and culture, viral PCR, cryptococcal antigen, and syphilis testing when relevant.

Limitations. Elevated lactate, creatine kinase and prolactin lack specificity. Normal CT and EEG do not exclude epilepsy. Interictal EEG abnormalities are common in older adults without seizures.

First aid. Time the event, move hazards away, place in the recovery position once convulsion ends, give oxygen, do not restrain, do not put anything in the mouth. Check glucose.

Seizure lasting 5 minutes or more, or repeated seizures without recovery

• Lorazepam 4 mg IV over 1 to 2 minutes (0.1 mg/kg, maximum 4 mg in a single dose), repeated once after 10 minutes. Monitor respiration, oxygen saturation and blood pressure. Reduce the dose in older adults and in hepatic impairment.
• If no IV access: midazolam 10 mg IM as a single dose for weight over 40 kg (5 mg for 13 to 40 kg), or midazolam 10 mg buccally. Alternative: diazepam 10 mg IV over 2 to 5 minutes, repeated once after 10 minutes (maximum 20 mg), or rectal diazepam 10 to 20 mg.
• If seizures continue 10 to 20 minutes after the second benzodiazepine dose, give one second line drug over 10 minutes: levetiracetam 60 mg/kg IV (maximum 4.5 g), or sodium valproate 40 mg/kg IV (maximum 3 g; avoid in pregnancy, liver disease and suspected mitochondrial disease), or phenytoin 20 mg/kg IV (maximum 2 g) at no more than 50 mg/minute (25 mg/minute in older adults or heart disease) with continuous ECG and blood pressure monitoring, in 0.9 percent sodium chloride only. Phenobarbital 15 mg/kg IV at 50 to 100 mg/minute is an alternative when others are unavailable, with airway support ready.
• Continuing seizures after a second line drug need anaesthetic and intensive care assessment for general anaesthesia.

Treat the provoking cause

• Hypoglycaemia (glucose under 4 mmol/L): 10 percent glucose 150 to 200 mL IV over 15 minutes, repeated until glucose is over 4 mmol/L, then an infusion. Give thiamine 500 mg IV before or with glucose when alcohol misuse or malnutrition is likely.
• Severe symptomatic hyponatraemia: 3 percent sodium chloride 150 mL IV over 20 minutes, repeated once or twice until sodium rises by 5 mmol/L or symptoms resolve. Limit the rise to 10 mmol/L in 24 hours (8 mmol/L when at risk of osmotic demyelination: alcohol, malnutrition, hypokalaemia, liver disease). Check sodium every 2 hours.
• Hypocalcaemia: calcium gluconate 10 percent 10 mL IV over 10 minutes with ECG monitoring.
• Eclampsia: magnesium sulphate 4 g IV over 5 to 15 minutes, then 1 g/hour for 24 hours after the last seizure; a further 2 g bolus for a recurrent seizure. Monitor patellar reflexes, respiratory rate (stop if under 12 breaths/minute), and urine output (over 100 mL in 4 hours); reduce the infusion in renal impairment. Antidote: calcium gluconate 10 percent 10 mL IV over 10 minutes. Control blood pressure and arrange delivery with obstetrics.
• Alcohol withdrawal: diazepam 10 mg IV over 2 minutes, repeated every 10 to 15 minutes until calm, with thiamine 500 mg IV every 8 hours for 3 days.
• Isoniazid toxicity: pyridoxine 5 g IV over 30 minutes, repeated if seizures recur, with benzodiazepines.
• Bacterial meningitis or encephalitis: ceftriaxone 2 g IV every 12 hours with dexamethasone 10 mg IV every 6 hours for 4 days; add ampicillin 2 g IV every 4 hours if age over 60 or immunocompromised; add aciclovir 10 mg/kg IV every 8 hours (adjust to creatinine clearance) for suspected encephalitis.
• Cerebral malaria: artesunate 2.4 mg/kg IV at 0, 12 and 24 hours, then once daily until oral therapy is tolerated, followed by a full oral artemisinin combination course; monitor glucose every 4 hours.
• Neurocysticercosis with viable parenchymal cysts: albendazole 15 mg/kg daily in 2 doses with food (maximum 800 mg daily) for 10 to 14 days, with prednisolone 1 mg/kg daily started before it; fundoscopy first to exclude retinal cysts; specialist only for numerous cysts or raised intracranial pressure.
• Raised intracranial pressure or mass lesion: neurosurgical referral.

Antiseizure medicine after a first unprovoked seizure. Treatment is not compulsory. Starting is reasonable when recurrence risk is high (epileptiform EEG, structural lesion on MRI, focal deficit, nocturnal seizure) or the patient prefers it. Early treatment reduces early recurrence but evidence of a better long term remission rate is limited. Select by seizure type.

• Focal seizures: lamotrigine or levetiracetam first; carbamazepine as an alternative.
• Generalised tonic clonic seizures: lamotrigine or levetiracetam; sodium valproate in men and in women who cannot become pregnant.
• Absence seizures: ethosuximide or sodium valproate; avoid carbamazepine and phenytoin, which can worsen absence and myoclonic seizures.

Dosing:

• Levetiracetam 500 mg orally twice daily, increased every 2 weeks by 500 mg twice daily to a usual 1 to 1.5 g twice daily; maximum 3 g daily. Creatinine clearance 50 to 79 mL/min: 500 to 1,000 mg every 12 hours; 30 to 49: 250 to 750 mg every 12 hours; under 30: 250 to 500 mg every 12 hours. Monitor mood, irritability and psychosis.
• Lamotrigine 25 mg orally daily for 2 weeks, then 50 mg daily for 2 weeks, then increased by 50 to 100 mg every 1 to 2 weeks to a usual 100 to 200 mg daily in monotherapy (maximum 500 mg daily). With valproate use half the schedule; with enzyme inducers use higher doses. Stop at the first sign of rash (Stevens Johnson syndrome). Oestrogen containing contraception lowers levels, and levels fall in pregnancy. Reduce the dose in hepatic impairment.
• Carbamazepine 100 to 200 mg orally once or twice daily, increased by 100 to 200 mg every 1 to 2 weeks to a usual 800 to 1,200 mg daily in 2 divided doses; maximum 1.6 g daily. Check sodium, full blood count and liver function at baseline and 2 to 4 weeks; HLA-B*1502 testing before use in people of Han Chinese, Thai or other South East Asian ancestry. Induces many drugs, including hormonal contraception and warfarin.
• Sodium valproate 600 mg orally daily in 2 doses, increased by 200 mg every 3 days to a usual 1 to 2 g daily; maximum 2.5 g daily. Monitor liver function, platelets, weight; check ammonia if new confusion. Do not use in women or girls who could become pregnant unless other drugs have failed and a specialist has agreed effective contraception.
• Ethosuximide 500 mg orally daily, increased by 250 mg every 4 to 7 days to a usual 1 to 1.5 g daily; maximum 2 g daily. Monitor blood count.

Special groups. Pregnancy: lamotrigine or levetiracetam preferred, folic acid 5 mg daily from before conception through the first trimester, monitor lamotrigine levels, and avoid valproate and topiramate. Enzyme inducing drugs make oral contraceptives unreliable; levonorgestrel intrauterine system or copper device are preferred. Breastfeeding is compatible with most antiseizure drugs.

Monitoring. Seizure diary, drug adverse effects, drug levels where useful (phenytoin, carbamazepine), bone health with long term enzyme inducers.

Referral and escalation. Neurology review within 2 weeks for every first seizure; same day for any red flag. Intensive care for refractory status. Epilepsy surgery assessment after failure of 2 appropriate drugs.

Admission criteria. Failure to return to baseline, status epilepticus, provoked seizure with a serious cause, abnormal examination, pregnancy, head injury, alcohol withdrawal, or poor home support. Discharge is reasonable after a first seizure when the patient is back to baseline, examination, glucose and electrolytes are normal, and follow up is arranged.

Discharge and safety netting. Advise no driving until cleared under local rules (many require 6 to 12 months seizure free), no swimming or bathing alone, no work at heights or with machinery. Return urgently for a seizure over 5 minutes, repeated seizures, injury, new weakness, speech change, fever or persistent confusion.