TABLE OF CONTENTS
The CT is done and you see an intracranial bleed.
And almost automatically, you write:
Inj. Levetiracetam 1 g IV stat
But pause for a second.
Is that always the correct thing to do?
Let’s unpack this question.
Firstly, what are you trying to prevent?
The short answer: Post-traumatic seizures (PTS).
But what exactly does that mean?
As the name suggests, post-traumatic seizures are seizures that occur after head trauma and are believed to be causally related to the injury itself [1].
PTS are broadly classified based on timing.
- Immediate seizures (<24 hours)
These occur within minutes or hours after injury.
A distinct subset occurs within seconds of impact, sometimes referred to as “concussive convulsions”.
Whether these events represent true epileptic seizures is debated. Some researchers consider them benign convulsive phenomena associated with concussion [2] while others include them in the category of early post-traumatic seizures because they may carry a similar risk of later epilepsy.
- Early seizures (<7 days)
These occur within the first week after injury and are generally considered provoked seizures, resulting from acute brain injury.
- Late seizures (>7 days)
Seizures occurring beyond the first week are considered unprovoked and usually represent post-traumatic epilepsy (PTE) [1].
This distinction matters clinically.
- Early seizures are acute symptomatic events with a relatively low risk of recurrence.
- Late seizures represent epilepsy, a more permanent structural and physiological change in the brain.
However, patients who experience early seizures do have a higher risk of developing post-traumatic epilepsy compared with those who do not [3].
But why do we care?
Post-traumatic seizures (PTS) are not rare after traumatic brain injury. In patients with severe blunt TBI, seizures occur in roughly 15% of cases.
They are typically distributed as:
- Immediate seizures (<24 hours): 1–4%
- Early seizures (<7 days): 4–25%
- Late seizures (>7 days): 9–42%
The concern is that seizures can contribute to secondary brain injury.
Seizure activity increases:
- cerebral metabolic demand
- excitatory neurotransmitter release
- intracranial pressure
Beyond the acute phase, post-traumatic seizures can also have long-term consequences, including:
- cognitive impairment
- behavioural changes
- reduced functional outcomes
- negative effects on employment and quality of life
In that sense, seizure-related neurotoxicity represents a potentially preventable source of morbidity.
However, the story is more nuanced. It is crucial to remember that :
- Antiepileptic medications are not risk-free, and routine prophylaxis must be balanced against potential adverse effects.
- More importantly, evidence suggests that reducing early post-traumatic seizures does not improve long-term mortality [4].
- Preventing early seizures does not prevent post-traumatic epilepsy [5].
- Antiseizure medications used in TBI only reduce early seizures (within the first 7 days) [5].
So while seizure prophylaxis can reduce early seizures, its impact on long-term outcomes remains limited, making careful patient selection essential.
Who is at risk?
Before discussing seizure risk, it helps to recall how traumatic brain injury (TBI) severity is classified.
According to ATLS (11th edition):
- Severe TBI: GCS ≤8
- Moderate TBI: GCS 9–12
- Mild TBI: GCS 13–15
The risk of post-traumatic seizures increases with increasing severity of brain injury.
Among all mechanisms, the highest seizure incidence occurs in penetrating traumatic brain injury.
Risk factors for early post-traumatic seizures
- Glasgow Coma Scale ≤10
- Immediate seizure after injury
- Cortical contusion
- Depressed skull fracture
- Penetrating head injury
- Subdural hematoma
- Epidural hematoma
- Intracerebral hematoma
- Post-traumatic amnesia >30 minutes
- Chronic alcoholism
Risk factors for late seizures (post-traumatic epilepsy)
- Early post-traumatic seizures
- Intracerebral hematoma
- Cortical contusion
- Severe TBI
- Prolonged loss of consciousness
- Post-traumatic amnesia >24 hours
Patients with
- Penetrating injuries
- Depressed skull fractures
- Cortical contusions
- Significant intracranial haemorrhage
represent the highest-risk group.
So, should you give seizure prophylaxis?
The short answer is: sometimes — but not for every patient with traumatic intracranial bleeding.
ACS guidelines suggest that patients with high-risk traumatic brain injury have a lower incidence of early post-traumatic seizures when given antiseizure medications [6].
- 14.2% early seizures in the placebo group
- 3.6% with phenytoin prophylaxis
However, this reduction did not translate into lower mortality or prevention of epilepsy [8].
The American Academy of Neurology (AAN) guidelines conclude that [7]
- Prophylactic phenytoin is effective in reducing early post-traumatic seizures in patients with severe TBI.
- However, antiepileptic prophylaxis does not reduce the risk of late seizures occurring after the first week.
In other words, antiseizure medications can prevent early seizures, but they do not prevent post-traumatic epilepsy.
So who should receive seizure prophylaxis?
Current recommendations from ATLS (11th edition) and the ACS Best Practices Guidelines for Traumatic Brain Injury (2024) suggest that seizure prophylaxis should be targeted to patients at higher risk of early post-traumatic seizures.
According to ATLS, prophylactic antiseizure medication is recommended in:
- Severe TBI
- Penetrating traumatic brain injury
- Moderate TBI with high-risk lesions, including:
- Depressed skull fracture
- Subdural hematoma (SDH)
- Epidural (extradural) hematoma
- Intracerebral hematoma
- Cortical contusion
- Seizure occurring within 24 hours of injury
The ACS 2024 TBI guidelines similarly recommend considering antiseizure prophylaxis as part of Tier 1 ICP management, typically for 7 days, unless another indication exists to continue therapy.
When prophylaxis is usually not recommended
ATLS also highlights several situations where routine seizure prophylaxis is not recommended, including:
- Mild TBI (GCS 14–15)
- Isolated traumatic subarachnoid haemorrhage (tSAH)
- Isolated traumatic intraventricular haemorrhage (IVH)
- Small isolated SDH with GCS ≥13
In these patients, the overall seizure risk is low, and the potential benefits of prophylaxis may not outweigh the risks of medication-related adverse effects.
What about mild and moderate TBI?
A 2024 systematic review and meta-analysis in JAMA Neurology found that seizure prophylaxis in mild and moderate TBI was associated with a small but statistically significant reduction in early post-traumatic seizures.
However, the absolute risk reduction was small, and the baseline incidence of early seizures in this population is already low.
This means the potential benefit must be weighed against:
- medication adverse effects
- unnecessary continuation beyond 7 days
- potential cognitive side effects, particularly in older patients [9]
For this reason, most guidelines still recommend selective rather than routine prophylaxis in mild TBI.
How long should prophylaxis be continued?
All major guidelines are consistent on this point.
Seizure prophylaxis should be continued for 7 days after traumatic brain injury.
Prophylactic antiseizure medication is stopped after 7 days, unless there is another indication to continue therapy, such as:
- A seizure occurring more than 24 hours after injury
- Pre-existing epilepsy requiring ongoing medication
- A neurosurgical or neurological indication to continue treatment
Importantly, studies have shown that prolonged administration of antiseizure medication beyond the first week does not reduce the risk of late post-traumatic seizures or post-traumatic epilepsy.
Which drug should you use?
ATLS takes a very pragmatic stance:
“The choice of antiseizure medication depends on availability.”
Several drugs have been studied for early post-traumatic seizure prophylaxis, including:
- Phenytoin
- Fosphenytoin
- Levetiracetam
- Valproic acid
- Lacosamide
Historically, phenytoin has been the most extensively studied agent, and the American Academy of Neurology (AAN) recommends it.
Why do many clinicians prefer levetiracetam
In modern practice, many clinicians favour levetiracetam over phenytoin.
The main reasons are practical.
Limitations of Phenytoin :
- requires therapeutic drug monitoring
- has multiple drug interactions
- is highly protein-bound
- requires monitoring of albumin levels and free drug concentrations
- can cause significant adverse drug reactions
Because of these challenges, its use in critically ill patients can be complex.
Advantages of Levetiracetam
- minimal drug interactions
- predictable pharmacokinetics
- no routine drug level monitoring required
- generally better tolerability
Typical dosing is: 10–20 mg/kg twice daily
Levetiracetam may cause behavioural adverse effects, particularly in patients with traumatic brain injury. Some clinicians use pyridoxine (vitamin B6) supplementation to mitigate these effects.
Drugs that should be avoided
Valproic acid is not recommended for early seizure prophylaxis in TBI.
Studies have shown that its use in this setting is associated with an increased risk of mortality compared with phenytoin.
What does the evidence say?
Current evidence suggests that levetiracetam and phenytoin have similar efficacy in preventing early post-traumatic seizures.
The PEACH randomised trial evaluated levetiracetam prophylaxis in intracerebral haemorrhage and suggested it may reduce acute seizures, although further studies are needed to determine whether this improves functional outcomes [11]
A brief word on post-traumatic epilepsy
Seizures that occur more than one week after a head injury are classified as late post-traumatic seizures and often represent the onset of post-traumatic epilepsy (PTE).
Unlike early seizures, which are usually related to acute brain injury and metabolic disturbances, late seizures reflect more permanent structural and physiological changes in the brain caused by trauma.
Traumatic brain injury is also one of the most important causes of symptomatic epilepsy in young adults, particularly in individuals aged 15–24 years.
However, an important principle should be remembered:
Antiseizure medications used in the acute phase of TBI do not prevent post-traumatic epilepsy.
Because of the lack of proven benefit and the potential for adverse drug effects, antiseizure medications are not recommended for long-term prophylaxis against epilepsy following traumatic brain injury.
Not every intracranial bleed needs levetiracetam — seizure prophylaxis should be guided by risk, not reflex.
What Matters
Before ordering levetiracetam in a trauma patient, ask three simple questions:
1️⃣ Did the patient have a symptomatic seizure after the injury?
This represents a post-traumatic seizure.
→ Treat with antiseizure medication
Common choice:
Levetiracetam 10–20 mg/kg twice daily
2️⃣Is there an indication for seizure prophylaxis?
Follow ATLS recommendations.
- Severe TBI
- Penetrating traumatic brain injury
- Moderate TBI with high-risk lesions, including:
- Depressed skull fracture
- Subdural hematoma (SDH)
- Epidural (extradural) hematoma
- Intracerebral hematoma
- Cortical contusion
- Seizure occurring within 24 hours of injury
→ Start seizure prophylaxis
3️⃣ Can we confidently rule out high seizure risk?
Low-risk scenarios include:
- Mild TBI (GCS 14–15)
- Isolated traumatic subarachnoid haemorrhage (tSAH)
- Isolated traumatic intraventricular haemorrhage (IVH)
- Small isolated SDH with GCS ≥13
→ If yes: No prophylaxis needed
→ If uncertain: Consider seizure prophylaxis
Want to Read More?
- Ritter, Anne C., et al. "Incidence and risk factors of posttraumatic seizures following traumatic brain injury: a traumatic brain injury model systems study." Epilepsia 57.12 (2016): 1968-1977.
- Haltiner, Alan M., et al. "Side effects and mortality associated with use of phenytoin for early posttraumatic seizure prophylaxis." Journal of neurosurgery 91.4 (1999): 588-592.
- Chang, Bernard S., and Daniel H. Lowenstein. "Practice parameter: antiepileptic drug prophylaxis in severe traumatic brain injury: report of the Quality Standards Subcommittee of the American Academy of Neurology." Neurology 60.1 (2003): 10-16.
- American College of Surgeons Committee on Trauma. Best Practices Guidelines for the Management of Traumatic Brain Injury. Chicago, IL: American College of Surgeons; 2024.
- Chang BS, Lowenstein DH. Practice parameter: Antiepileptic drug prophylaxis in severe traumatic brain injury. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2003;60(1):10-16. doi:10.1212/01.WNL.0000031432.05543.14.
- Pease M, Mittal A, Merkaj S, et al. Early Seizure Prophylaxis in Mild and Moderate Traumatic Brain Injury: A Systematic Review and Meta-Analysis. JAMA Neurol. 2024;81(5):507–514. doi:10.1001/jamaneurol.2024.0689
- Atwood, Rex, et al. "Use of levetiracetam for post-traumatic seizure prophylaxis in combat-related traumatic brain injury." Military medicine 188.11-12 (2023): e3570-e3574.
- Peter-Derex, Laure, et al. "Safety and efficacy of prophylactic levetiracetam for prevention of epileptic seizures in the acute phase of intracerebral haemorrhage (PEACH): a randomised, double-blind, placebo-controlled, phase 3 trial." The Lancet Neurology 21.9 (2022): 781-791.
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