Seizures
Classification
- Early: < 7 days of injury
- Early PTS have not been associated with worse outcomes.
- Late: > 7 days following injury
- True Post traumatic epilepsy
Due to
- Neurochemical disarray
EEG
- Demonstrates that the majority of seizures do not have overt motor manifestations and require continuous monitoring of seizure activity.
- ECoG recordings can distinguish the hallmark slow potential change of CSD from seizures;
- While CSD and seizures frequently occur together, there is no correlation between the two phenomena in regard to time, space, and intensity (Fabricius, 2006).
Numbers
- Overall average risk of PTS after HI=2% in 10 yrs
- Mild TBI
- Clinical PTS: similar to without HI
- Moderate TBI
- Clinical PTS: 5%
- Severe TBI, the rate of
- Clinical PTS: 12%,
- Subclinical seizures (via EEG): 20% to 25%.
- Following moderate to severe TBI,
- Seizures occur in more than 20% of patients in the first week;
- Peak incidence is bimodal
- Early peak at 29 hours
- Later peak at 140 hours,
- Mean duration of 2.8 minutes
- A tendency to cluster.
The risk factors for early PTS include:
- Acute subdural, epidural. or intracerebral hematoma (SDH, EDH or ICH)
- Risk of seizure >20%
- Open-depressed skull fracture with parenchymal injury
- Seizure within the first 24 hrs after injury
- Risk of seizure >20%
- Glasgow Coma Scale score< 10
- Risk of seizure after Severe TBI (GCS <8): 15%
- Penetrating brain injury
- Risk of seizure >20%
- History of significant alcohol abuse
- ± Cortical (hemorrhagic) contusion on CT
During seizures
- ICP is secondarily elevated, with the ictal ICP being higher than interictal ICP.
- This is due to
- Prolonged increases in CBF,
- Increases to extracellular oedema,
- Glutamate accumulation in the interstitium.
- Can lead to
- Increase risk for swelling
- Stimulation of glycolysis and neurochemical changes that may further stress neuronal integrity.
Lactate pyruvate ratio (LPR)
- Microdialysis LPR is higher
- For TBI patients with seizures (compared to without)
- During the ictal periods (compared to interictal periods).
- Increased LPR is associated with prolonged metabolic stress
- Therefore seizure control is a therapeutic target for minimizing metabolic stress postinjury.
Higher risk of seizure
- Severe TBI
- Focal seizures with secondary generalization occur in 78% of reported seizures after severe TBI.
- Presence of a brain contusion
- Pericontusional regions, in particular in the frontotemporal region, are electrically active and capable of epileptiform activity.
- Presence of subdural haematoma
Reducing risk of seizure
- Early evacuations of mass lesions may be associated with reduced seizure activity
- Anti-epileptics (phenytoin/keppra)
- Reduces short term (7 days) but not long term seizure.
Outcome
- Early PTS during acute hospitalisation have been shown to be an independent risk factor for PTS within 12 and 24 months following TBI.
- Late PTS within 24 months can have a negative impact on quality of life, return to work, return to driving, and can even result in death.
Beta- amyloid deposition and apolipoprotein E interaction
Mechanism
- After TBI → Aβ concentrations and apolipoprotein E (ApoE) concentration drops → Apolipoprotein E (ApoE) used to form ApoE-lipid complexes to repair neurons → later on there is an increase production of ApoE → for whatever reason which lead to formation of ApoE-Abeta complexes that deposit intra- axonal in the brain parenchyma → lead to neuronal damage → poorer recover of TBI and accelerated degen of brain (Alzheimer)
- Long- term follow- up of patients with TBI also correlated with incidence of Alzheimer’s disease,
- ApoE isotype as a key predictor.
TBI is shown to trigger pathological production and accumulation of amyloid- (Aβ) peptides
- Cleavage of amyloid precursor protein (APP) produces
- Apolipoprotein E (ApoE)
- ApoE ε4
- Carries greater risk for Aβ burden
- ApoE ε4 binds the least avidly to cytoskeletal proteins that would promote neurite growth and neuroprotective effect.
- ApoE ε4 binds more avidly to Aβ and promotes aggregation into amyloid fibrils.
- 6 months after TBI
- 57% of patients have unfavourable outcome (GOS: dead, vegetative state, or severe disability)
- ApoE ε3
- (More frequent)
- Reduce the risk for Aβ burden
- ε2
- (Rare)
- Reduce the risk for Aβ burden.
- 6 months after TBI
- 27% of patients have unfavourable outcome
- Neuroprotective against cerebral ischaemia,
- Intraventricular infusion of ApoE reduced neuronal damage after ischaemia in animal models via clearance of lipid and cholesterol debris.
- Anti-inflammatory
- Effects through downregulation of microglia and cytokine release
- Aβ
The polymorphism of the ApoE gene determines the risk for plaque deposition:
Function
- Higher risk
- Types of injury
- DAI
- Intracranial microdialysis measured high levels of Aβ in patients with DAI compared to focal injuries
- Contusional and pericontusional regions
Development of post-traumatic epilepsy
- Pediatric traumatic brain injury → epileptogenic injury → pathophysiologic mechanisms → acute biomarkers (critical care) → latent period → post-traumatic epilepsy
- Pathophysiologic mechanisms
- Blood brain barrier disruption
- Impaired cerebrovascular pressure reactivity
- Autonomic dysfunction
- Neuronal loss
- Glial changes
- Altered neuronal excitability
- Astrocyte reorganization
- Synaptic plasticity
- Acute biomarkers (critical care)
- Elevated intracranial pressure
- Impaired cerebrovascular pressure reactivity (elevated PRx, wPRx indices)
- Decreased heart rate variability (HRsd)
- Increased seizure burden
- Seizures > 24 hours post-injury
- Interictal epileptiform discharges
- Sleep spindle abnormalities
- Worsened neuroimaging (increased CT marshall scores)
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