Generalised tonic-clonic seizures and convulsive status epilepticus

Last updated: October 2024

 

Generalised tonic-clonic seizures are involuntary movements of both sides of the body associated with impaired or loss of consciousness. They result from abnormal brain activity.

 

Most seizures are brief (less than 5 minutes) and resolve spontaneously. They may occur once or may recur.

 

In young children, seizures frequently occur in the context of fever, with no underlying causes. These are defined as "febrile seizures".

 

A seizure lasting longer than 5 minutes or 2 or more seizures in 5 minutes without complete restoration of baseline consciousness between seizures is defined as "status epilepticus" [1] Citation 1. Lowenstein DH, Bleck T, Macdonald RL. It’s Time to Revise the Definition of Status Epilepticus. Epilepsia. 1999;40(1):120-122. 
https://doi.org/10.1111/j.1528-1157.1999.tb02000.x [2] Citation 2. Brophy GM, Bell R, Claassen J, et al. Guidelines for the Evaluation and Management of Status Epilepticus. Neurocrit Care. 2012;17:3-23.
https://higherlogicdownload.s3.amazonaws.com/NEUROCRITICALCARE/b8b3b384-bfb9-42af-bb55-45973d5054a4/UploadedImages/Documents/Guidelines/SE_Guidelines_NCS_0412.pdf . Status epilepticus is a medical emergency requiring immediate management. The longer a seizure lasts, the more difficult it is to stop, and the greater the risk for permanent brain damage and death.

 

In pregnancy and the postpartum period, seizures may be a manifestation of eclampsia. Refer to Essential obstetric and newborn care, MSF. 

Clinical features

During a seizure

• contraction of muscles, including respiratory muscles (tonic phase), followed by rhythmic jerking of the arms and legs (clonic phase)

and

• loss of consciousness

These signs may be associated with loss of urine, breathing difficulty, and cyanosis.

 

Immediately after a seizure (postictal phase)

The patient experiences fatigue and temporary symptoms such as confusional state, headache, memory loss, focal deficits. Recovery usually occurs within 30 to 60 minutes [3] Citation 3. Pottkämper JCM, Hofmeijer J, Van Waarde JA, Van Putten MJAM. The postictal state — What do we know? Epilepsia. 2020;61(6):1045-1061.
https://doi.org/10.1111/epi.16519 but may be delayed.

First aid during a seizure

• Note the time. Call for help.
• Protect from falls and trauma, loosen clothing.
• Maintain airway, place patient in recovery position to avoid aspiration, do not put anything in the mouth.
• Treat hypoglycaemia if present or administer glucose if unable to measure capillary blood glucose immediately (see Hypoglycaemia, Chapter 1).

• Depending on the context:

  • Administer oxygen if available.

  • If febrile seizures are likely, see Febrile seizures.

  • In adults, thiamine (100 mg by IV infusion in 100 ml 0.9% NaCl over 30 minutes) may be administered at the same time as glucose if vitamin B₁ deficiency is suspected (e.g. in case of alcohol-related seizures) a Citation a. Thiamine should be administered at the same time as glucose because glucose may precipitate Wernicke's encephalopathy in patients with chronic alcohol consumption. Treatment should be continued for 3 to 5 days with thiamine PO (100 to 200 mg once daily) or IM (100 mg once daily). .

• If seizures stop spontaneously in 5 minutes or less, see Postictal management.

Febrile seizures

Febrile seizures frequently occur in children aged 6 months to 5 years with fever (usually due to viral infection) and no signs of central nervous system (CNS) infection, metabolic disturbances, or history of afebrile seizures [4] Citation 4. Steering Committee on Quality Improvement and Management, Subcommittee on Febrile Seizures. Febrile Seizures: Clinical Practice Guideline for the Long-term Management of the Child With Simple Febrile Seizures. Pediatrics. 2008;121(6):1281-1286.
https://doi.org/10.1542/peds.2008-0939 . They may be either "simple" or "complex".

 

 

• A simple febrile seizure is defined as a single generalised seizure, without focal signs, that lasts less than 15 minutes, and does not recur within a 24-hour period [4] Citation 4. Steering Committee on Quality Improvement and Management, Subcommittee on Febrile Seizures. Febrile Seizures: Clinical Practice Guideline for the Long-term Management of the Child With Simple Febrile Seizures. Pediatrics. 2008;121(6):1281-1286.
  https://doi.org/10.1542/peds.2008-0939 . Most of these seizures last less than 5 minutes and if so, no antiseizure treatment is required. The risk of subsequent epilepsy is low after this type of seizure. Observe the child at least until full recovery, and discharge when child returns to neurological baseline. Give instructions for home-based management: symptomatic treatment of fever to make the child more comfortable (see Fever, Chapter 1) and of underlying viral infection if relevant.

 

• A complex febrile seizure is a seizure meeting at least one the following criteria: presence of focal signs, a duration more than 15 minutes, or multiple seizures within a 24-hour period [4] Citation 4. Steering Committee on Quality Improvement and Management, Subcommittee on Febrile Seizures. Febrile Seizures: Clinical Practice Guideline for the Long-term Management of the Child With Simple Febrile Seizures. Pediatrics. 2008;121(6):1281-1286.
  https://doi.org/10.1542/peds.2008-0939 . 

 

• In all cases:
  • Provide first aid during a seizure.
  • After a seizure, see Postictal management.
  • If a seizure lasts more than 5 minutes or recurs within 5 minutes, start treatment for status epilepticus.

Status epilepticus

In case of status epilepticus, start antiseizure medication (ASM).

 

Step 1 - First-line ASM treatment

• Administer one of the following benzodiazepines (BZD). The choice depends on the situation, i.e. if seizures occur in pre-hospital or hospital setting.
• In any case, do not administer more than 2 doses of BZD.

Status epilepticus in pre-hospital setting

• Administer midazolam (5 mg/ml solution) by buccal or intranasal route or diazepam (5 mg/ml solution) by rectal route. For doses to be administered, see Table 1.
• If seizures do not stop 5 minutes after the first dose of BZD, readminister the same dose. 
• If seizures do not stop after the second dose of BZD, refer urgently to hospital for treatment with second-line ASM(s).
• If seizures stop after 1 or 2 doses of BZD, refer to hospital for further management (aetiologic treatment and potential maintenance treatment).
• While awaiting transfer, monitor vital signs, administer oxygen if available to maintain SpO₂ > 94%. If seizures stop, see Postictal management.

Status epilepticus in hospital setting

Check whether a BZD has been administered before arrival at the hospital and the number of doses. If one dose was administered, give a second dose. If 2 doses were administered, start Step 2 - Second-line ASM treatment.

 

If no pre-hospital dose of BZD was administered:

• If IV or IO access: diazepam (5 mg/ml solution) by slow IV injection (over 3 to 5 minutes). For doses to be administered, see Table 1.
• If no IV or IO access: midazolam (5 mg/ml solution) by buccal or intranasal route or midazolam (1 mg/ml solution) by IM route or diazepam (5 mg/ml solution) by rectal route. For doses to be administered, see Table 1.
• If seizures do not stop 5 minutes after the first dose of BZD, readminister the same dose. 
• If seizures do not stop after the second dose of BZD, start Step 2 - Second-line ASM treatment.
• If seizures recur: 
  • 6 hours or more after seizures stop, restart treatment from Step 1 - First-line ASM treatment as for a new seizure,
  • Less than 6 hours after seizures stop, continue treatment at the last point, e.g.:
    • if seizures recur < 6 hours after a first dose of BZD, readminister the same dose,
    • if seizures recur < 6 hours after 2 doses of BZD, start Step 2 - Second-line ASM treatment.
• If seizures stop after 1 or 2 doses of BZD and do not recur, see Postictal management and evaluate the need for maintenance ASM treatment.

 

Table 1 - Dosage of benzodiazepines

 

Age	1 to < 4 months	4 to < 12 months	1 to < 3 years	3 to < 5 years	5 to < 9  years	9  to < 12 years	≥ 12 years  adults
Weight	3 to < 6 kg	6 to < 10 kg	10 to < 15 kg	15 to < 20 kg	20 to < 30  kg	30 to < 40  kg	≥ 40 kg
midazolam buccal (a) Citation a. Midazolam buccal route: lay the patient on their side. Withdraw the required dose using a 1 ml or 2 ml syringe. Remove the needle. Insert the tip of the syringe into the space between the gum and cheek. Administer the dose by slowly pushing the syringe plunger.  or intranasal route (b) Citation b. Midazolam intranasal route: lay the patient on their back or side. Withdraw the required dose using a 1 ml or 2 ml syringe (add an additional 0.1 ml to the calculated dose to account for the remaining liquid in the atomising device). Remove the needle. Attach the intranasal atomisation device to the syringe. Briskly push the syringe plunger to spray the dose into the nostril. The dose can be split in both nostrils to reduce irritation.  , dose in ml (5 mg/ml solution)
	0.25 ml	0.4 ml	0.6 ml	1 ml	1.2 ml	2 ml	2 ml
midazolam IM route, dose in ml (1 mg/ml solution)
	0.6 ml	1.2 ml	2 ml	3 ml	4 ml	6 ml	10 ml
diazepam rectal route (c) Citation c. Diazepam rectal route: lay the patient on their side. For volumes up to 1 ml, use a 1 ml syringe. Withdraw the required dose. Remove the needle. Insert the syringe into the rectum for a length of 1 to 3 cm (depending on age) to administer the dose. For volumes greater than 1 ml, use a 2 ml syringe and attach to the tip of the syringe a nasogastric tube n°8 cut to a length of 2 to 3 cm to administer the dose. After administration, hold the buttocks together for at least one minute. , dose in ml (5 mg/ml solution)
	0.4 ml	0.7 ml	1.2 ml	1.5 ml	2 ml	2 ml	2 to 4 ml (d) Citation d. In patients ≥ 65 years: for diazepam rectal, do not exceed 2 ml (= 10 mg) per dose; for diazepam IV, reduce the dose by half (1 ml = 5 mg per dose).
diazepam slow IV route, dose in ml (5 mg/ml solution)
	0.25 ml	0.4 ml	0.6 ml	1 ml	1.2 ml	2 ml	2 ml (d) Citation d. In patients ≥ 65 years: for diazepam rectal, do not exceed 2 ml (= 10 mg) per dose; for diazepam IV, reduce the dose by half (1 ml = 5 mg per dose).

Step 2 - Second-line ASM treatment

• If seizures do not stop after second-line ASM, change to another second-line ASM.
• If seizures do not stop or recur in < 6 hours despite 2 second-line ASMs, transfer the patient to an intensive care unit for treatment of refractory status epilepticus.
• If seizures stop after 1 or 2 second-line ASM(s), see Postictal management and Maintenance ASM treatment.

Patients with known epilepsy

• History taking:
  • ASM and dose taken, effectiveness.
  • Missed doses if any, and reason (e.g. forgetting, interruption due to adverse effects, shortage of medication).
• Management:
  • Administer the IV loading dose of the medication that the patient should usually take or see Table 2.
  • If seizures do not stop, continue treatment as for patients with no known epilepsy.
  • If seizures stop after 1 or 2 second-line ASM(s), see Postictal management and Maintenance ASM treatment.

Step 3 - Maintenance ASM treatment 

Some patients may require maintenance treatment after the loading dose.

 

• In children, maintenance treatment is indicated when:
  • a second-line ASM has been used to control seizures, unless a reversible cause of seizure can be quickly treated (e.g. hypoglycaemia, electrolyte disturbances),
  • 3 or more seizures occur within a 24-hour period,
  • focal signs and/or impaired consciousness persist beyond expected postictal period,
  • there is known or presumed traumatic brain injury (within 24 hours of injury),
  • there is known or presumed epilepsy.

Unless the child has already received a loading dose, start with a loading dose, see Table 3.

 

• In adults, maintenance treatment is indicated for all patients, unless a reversible cause of seizure can be quickly treated (e.g. hypoglycaemia, electrolyte disturbances).

 

• If seizures do not recur, administer maintenance treatment for 48 to 72 hours and then reassess. Use oral route (or nasogastric tube). For maintenance doses to be administered, see Table 3.
• For seizures in the context of head trauma, maintenance treatment should last 7 days.
• In case of epilepsy, start or resume long-term treatment. See Epilepsy, Chapter 12.

Postictal management

Frequent causes of seizures

• Febrile seizures: in young children with fever, usually in a context of a respiratory or gastrointestinal viral infection.
• CNS infections: e.g. any meningitis (for Bacterial meningitis, see Chapter 7); severe malaria, neurocysticercosis, trypanosomiasis (see Chapter 6); cerebral toxoplasmosis, cryptococcal meningitis (see HIV infection and AIDS, Chapter 8).
• Metabolic abnormalities: e.g. hypoglycaemia (Chapter 1), electrolyte disorders (hyponatremia, hypocalcaemia).
• Intoxications: e.g. psychoactive drugs and alcohol, methanol, medications, neurotoxic pesticides and venoms, carbon monoxide.
• Withdrawal from CNS depressants: e.g. alcohol (see Agitation and Acute confusional state, Chapter 11), opioids, benzodiazepines, barbiturates.
• Use of seizure-provoking drugs: many drugs may be involved, e.g. antidepressants, antipsychotics, some antimicrobials.
• Vitamin B deficiencies (thiamine and pyridoxine), particularly in patients with chronic alcohol consumption.
• Epilepsy: undiagnosed epilepsy, poor adherence to treatment, ineffective treatment or abrupt stop of ASM.
• Head trauma, CNS tumour, stroke, sepsis, encephalopathy (e.g. hypertensive, hypoxic).