ISCHEMIC STROKE

Stroke-related epilepsy (STRE)

• stroke, both ischemic and hemorrhagic, is a significant cause of seizures, especially in the elderly patients
  • stroke accounts for ~ 50% of newly diagnosed seizures among the elderly
  • stroke patients have about an 11.5% risk of single or recurrent seizures in the first 5 years after a stroke (Burn, 1997)
    
  • the incidence and prevalence of post‐stroke seizures and post‐stroke epilepsy are likely to rise in the future
  • seizures may occur as a consequence of any type of stroke (ischemic stroke, intracerebral and subarachnoid hemorrhage, and cerebral sinus thrombosis with venous infarction)
• stroke-related (post‐stroke) seizures and stroke-related (post‐stroke) epilepsy (STRE) are common causes of hospital admissions
  • they generally have a favorable prognosis and can be effectively managed using antiseizure medication (ASM)
    
  • < 25% of cases become drug-resistant
  • seizures may result in increased morbidity, longer hospital stays, significant disability after discharge, and higher resource utilization
• controlled trials are needed to explore the primary and secondary prevention of STRE and to provide high-quality evidence on the efficacy and tolerability of ASM to guide treatment

The classification of post‐stroke seizure (stroke-related seizure) and post‐stroke epilepsy (stroke-related epilepsy) follows a two-step process:

• classification of seizures according to standardized diagnostic (revised) guidelines of the International League Against Epilepsy (ILAE)
• determination of the relation of the seizures to the cerebrovascular event
  • stroke-related seizures – isolated or infrequent seizures that occur as a direct result of a stroke and may be early or late-onset
    • early-onset seizures (within 7-14 days of stroke onset, with a peak within 24 hours)
      • the time frame varies in different clinical definitions and reports; generally, they occur soon after stroke onset
      • early-onset seizures belong to acute symptomatic seizure (ASS)
        
      • early seizures are believed to be the consequence of local metabolic disturbances
        
    • late-onset seizures (> 7-14 days after stroke onset)
      • late seizures are thought to occur when the brain has acquired a predisposition to seizures
      • late-onset seizures have a higher recurrence rate
  •  stroke-related epilepsy (STRE)
    • refers to recurrent seizures attributed to a stroke, indicating a chronic condition that requires long-term management (often with antiseizure medications)
    • STRE develops in about 1/3 of early-onset and 50% of late-onset seizures  (Olsen, 2001)

• early-onset seizures after ischemic strokes are often caused by metabolic disorders
  • increase in intracellular Ca²⁺ and Na⁺ with a resulting lower threshold for depolarisation, glutamate excitotoxicity, hypoxia, metabolic dysfunction, global hypoperfusion
  • seizures after hemorrhagic strokes are thought to be attributable to irritation caused by products of blood metabolism
• late-onset seizures and STRE are associated with persistent changes in neuronal excitability and gliotic scarring that disrupt the normal neuronal network
  • these changes can lead to hyperexcitability and epileptogenic foci
  • the location and extent of the cerebral insult significantly influence the risk of epilepsy
  • hemosiderin deposits after a hemorrhagic stroke are thought to be the cause of an increased irritability
    

• key risk factors associated with a higher incidence of post‐stroke seizures include
  • stroke severity
  • multiple / larger lesions
  • cortical lesion or hippocampal involvement
  • hemorrhagic strokes
    • ICH: parenchymal location, presence of malformation
    • SAH: MCA aneurysm, concomitant intraparenchymal hematoma
  • pre-existing structural brain conditions
  • patient age
• early-onset seizures increase the risk of developing epilepsy

• diagnosis involves a comprehensive assessment, including:
  • patient history
  • neurological examination
  • electroencephalography (EEG)
    • EEG is crucial in differentiating epileptic seizures from other phenomena, such as TIAs or migraine auras
    • EEG may be normal in about 5% of cases ⇒ normal EEG does not exclude epileptogenicity
    • focal spikes or periodic bilateral discharges are associated with a higher risk of seizures
  • neuroimaging
    • essential for identifying the epileptogenic zone and assessing the extent of brain damage
    • MRI brain is the imaging modality of choice, as it shows a number of abnormalities that may be missed on CT (cortical malformations, hippocampal sclerosis, small mass lesions, and temporal lobe cavernomas)

• antiseizure medications (ASMs) remain the mainstay of epilepsy management in all age groups
• stroke etiology, side effect profiles, and patient comorbidities should be considered when selecting the appropriate drug
  • newer AEDs with fewer side effects and drug interactions are preferable, such as levetiracetam (LEV)
    
• non-pharmacological interventions, such as surgery, may be considered in drug-resistant cases
• the general principles used for managing other types of epilepsy also apply to post-stroke seizures and epilepsy
  • inform the driving licence agency
  • advice on supervision of activities such as swimming, cooking, etc
  • schedule regular follow-ups to monitor for and address any potential drug side effects

• specific prevention of post-stroke epilepsy is not possible
• however, recanalization therapy and treatment and prevention of complications may reduce the extent of permanent brain damage (extent of lesion and stroke severity are significant risk factors for STRE)