• stroke, both ischemic and hemorrhagic, is a significant cause of seizures, especially in the elderly
    • stroke is the cause of ~ 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 increase
    • seizures may occur as a consequence of all stroke types (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, either as a presenting feature or as a complication of stroke
    • they generally have a good prognosis and can be well controlled with anticonvulsants
    • < 25% of cases become drug-resistant
    • seizures may result in increased morbidity, longer hospital stays, greater disability at 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 antiseizure medications (ASMs) to guide treatment

Classification

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 – singular 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 are a type of 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 peak within 6-12 months after the stroke and have a higher recurrence rate of up to 90%
    •  stroke-related epilepsy (STRE)
      • refers to recurrent seizures attributed to a stroke, indicating a chronic condition requiring 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)
  • acute symptomatic seizures (ASS) occur in close temporal association with an acute cerebral insult or disturbance
  • the time frame for ASS is typically within 7 (14) days of the event (such as stroke, traumatic brain injury, metabolic disorder, or infection)
  • ASS is directly related to the transient disturbance caused by the acute condition

Pathophysiology

  • 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

Risk factors

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

Clinical presentation and diagnostic evaluation

Clinical presentation

  • post‐stroke seizures typically follow a localization-related semiology
    • ~ 2/3 present with focal seizures
    • generalized tonic‐clonic seizures are more common with late-onset seizures
    • status epilepticus develops in less than 10% of cases
  • it may not be always clear whether the patient is having seizures
    • post‐stroke seizure, particularly in older people, may present with acute confusion, slowing, behavioral changes, and syncope. These symptoms also frequently lead to a misdiagnosis of stroke recurrence, especially when the patient has postictal paresis (Todd’s paralysis)
    • consider atypical presentations of seizure and stroke mimics

Diagnostic evaluation

  • diagnosis involves a comprehensive assessment, including:
    • patient history
    • neurological examination
    • electroencephalography (EEG)
      • EEG is crucial in differentiating epileptic seizures from other post-stroke 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)

Management

  • 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 of management used for epilepsy of any cause also apply to the management of post‐stroke seizures and post‐stroke epilepsy
    • inform the driving licence agency
    • advice on supervision of activities such as swimming, cooking, etc
    • regular follow-up for monitoring of drug side effects

Choice of antiseizure medications

  • in the acute phase, choose valproic acid (VPA), levetiracetam (LEV), and lacosamide(LCM), as they allow rapid parenteral titration
  • phenytoin (PHE) has potential interactions with anticoagulants
  • for long-term medication, consider carbamazepine (CBZ), VPA, LEV

Duration of antiseizure medications

  • optimal duration of antiseizure medication (ASM) is unknown
  • risk of epilepsy is approx. 5-11% (higher in patients with parenchymal hemorrhages and focal neurological deficits)
    • most late-onset seizures occur within the first year
    • late-onset seizures are more common in patients with early-onset seizures
  • duration should be guided by stroke etiology, the presence and extent of parenchymal lesions, EEG findings, and the timing of epileptic seizures (early x late)
  • no strict recommendation; an individualized approach is advised to avoid unnecessary long-term ASM use
    • isolated symptomatic seizure (<2 weeks after stroke onset) without large parenchymal lesion ⇒ AED therapy can be gradually tapered within 2-4 weeks after the acute phase
    • isolated symptomatic seizure or multiple ASS with parenchymal lesion and/or pathological EEG ⇒ continue ASM treatment for up to 12 months
    • post-stroke epilepsy (at least two seizures > 2 weeks after stroke onset) ⇒ long-term ASM is reasonable

Prophylactic use of antiseizure medications

  • ischemic stroke: prophylactic use of antiseizure medication (ASM) is not recommended for ischemic stroke (AHA/ASA 2013 III/C)
  • CVST: prophylactic treatment in the first 7-14 days after diagnosis of CVST may be considered (based on the ICSVT study cohort results)
    • patients with hemiparesis and parenchymal lesions are at higher risk for ASS
    • prophylactic treatment does not lower the risk of post-CVST epilepsy
  • SAH: prophylactic antiseizure medication is not routinely recommended; prophylactic treatment in the first 7-14 days may be considered in individual cases to prevent aneurysm rupture during the seizure
  • ICH: prophylactic antiseizure medication is not routinely recommended

Prevention

  • 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 risk factors for STRE)

Related Content

You cannot copy content of this page

Send this to a friend
Hi,
you may find this topic useful:

Stroke-related epilepsy (STRE)
link: https://www.stroke-manual.com/stroke-related-epilepsy-stre/