• seizure is defined as a transient occurrence of signs and/or symptoms resulting from abnormal synchronous (epileptic) neuronal activity in the brain
    • seizures can affect behavior, movements, sensations, and levels of consciousness
  • acute symptomatic seizures (ASS) occur in close temporal association with an acute cerebral insult or disturbance and account for about 40% of first seizure episodes
    • the time frame for ASS is typically within 7-10 (14) days of the event (such as stroke, traumatic brain injury, metabolic disorder, or infection)
    • unlike epilepsy, which involves recurrent seizures without an apparent immediate cause, ASSs are directly related to the transient disturbance caused by the acute condition
  • the risk of ASS is influenced by the nature and location of the cerebral disorder as well as other factors (genetics, age, comorbidities)
  • continuous EEG (cEEG) can be used to predict the occurrence of symptomatic seizures  (2HELPS2B)
  • ASSs do not include:
    • seizures triggered by specific stimuli (e.g., visual) that commonly occur in patients with epilepsy
    • seizures triggered by sleep deprivation (sleep deprivation is not an independent triggering factor in the development of ASSs)

Acute symptomatic seizures are directly related to an acute insult or condition, while epilepsy is a chronic disorder characterized by recurrent unprovoked seizures

Etiology

Structural brain lesions
  • stroke (25-30%)
    • ischemic stroke, ICH, venous sinus thrombosis, SAH
  • head trauma (15%)
  • neurosurgical operations
  • tumors
Toxic-metabolic disorders
  • hypo- Ca, Mg, Na
  • alkalosis
  • hypoglycemia, hyperglycemia (nonketotic and with ketoacidosis)
  • hyperammonemia
  • uremia, hemodialysis
  • alcohol abuse
  • drugs (cocaine, amphetamines, cannabinoids)
  • medications
    • related to use (see below)
    • related to withdrawal (barbiturates, benzodiazepines)
Inflammation
  • brain abscess
  • herpetic encephalitis
  • meningitis
  • HIV-related encephalopathy
Others
  • CO intoxication
  • hypoxic encephalopathy
  • hypertensive encephalopathy, eclampsia
  • pyridoxine deficiency
  • hypo- and hyperthyroidism
  • according to various sources, 25-60% of all ASSs
    • 50-70% of ASSs occur in the first 48 hours after the onset of stroke
  • more common in patients with bleeding and dural sinus thrombosis
  • especially in hemorrhage, continuous EEG monitoring is recommended in the acute stage → significantly higher detection rate of clinically unrecognized seizures and NCSE
  • ASS risk increases with more extensive lesions and cortical involvement; in SAH, a relationship with the amount of blood in the basal cisterns has been described
  • prophylactic administration of anti-seizure medication (ASM) is not recommended (AHA/ASA 2019 III/C-LD)
  • continuous EEG monitoring shows a higher incidence of ASS (mainly non-convulsive) in moderate to severe TBI
  • most seizures occur within 24 hours after injury
  • the risk of ASS or epilepsy depends on the severity of the injury and is higher in hemorrhage (SDH, EDH, or parenchymal – 7-10%), as well as in impressive calvary fractures and contusion injuries
  • laboratory abnormalities occur in temporal relationship with seizures; both the absolute value and the speed at which the disorder develops play important roles
  • uremia or electrolyte imbalance may play a role in renal failure; seizures occur in hemodialysis patients due to:
    • uremic encephalopathy
    • dysequilibration syndrome
    • hypocalcemia
    • hypoglycemia
    • hyponatremia
  • ASSs are uncommon in hepatic failure and are related to hyperammonemia
  • ASSs occur in patients with hyponatremia, hypomagnesemia, and hypocalcemia 
hypoglycemia     glucose < 2,0 mmol/l
hyperglycemia with ketoacidosis    glucose > 25 mmol/l
hypomagnesemia     Mg < 0,3 mmol/l
hypocalcemia     Ca2+ < 1,2 mmol/l
hyponatremia     Na < 115 mmol/l
renal failure
    urea > 35.7 mmol/l
    creatinine > 884 umol/l
  • high risk of ASS and epilepsy is associated with brain abscess and herpetic encephalitis
  • alcohol
    • ASSs are most commonly associated with withdrawal syndrome (in regular consumption > 5 g/day) (⇒ Alcohol Withdrawal Seizure – AWS)
    • seizures occur between 7-48 hours, often in combination with delirium
    • clustered seizures or even ASSE may occur
    • in chronic alcoholics, it is necessary to rule out concurrent metabolic disorders (hypoglycemia, hyponatremia, etc.) and consider structural brain lesions (hemorrhage, trauma, etc.)
  • medications
    • dose-dependent effect, often due to intoxication (intentional or unintentional)
    • higher risk associated with polypharmacy and more common in older patients
    • ASS and SE can also occur during drug withdrawal (barbiturates, benzodiazepines, opioids, baclofen, vigabatrin)
  • drugs (cocaine, amphetamines, cannabinoids)
Drugs with the risk of developing ASS when used in therapeutic dose
neuroleptics phenothiazines (chlorpromazine), haloperidol, clozapine
antidepressants tricyclics, maprotiline, clomipramine, SNRIs (venlafaxine), SSRIs (fluoxetine, sertraline)
antibiotics beta-lactams (penicillins), fluoroquinolones, metronidazole
analgesics meperidine and normeperidine, tramadol, fentanyl and sufentanil, morphine intrathecally
anesthetics sevoflurane, propofol
cytostatics 5-fluorouracil, busulfan, chlorambucil, methotrexate
antiasthmatics theophylline
immunosuppressants cyclosporine
antihistamines diphenhydramine
muscle relaxants baclofen
antiulcer drugs cimetidine

Clinical presentation

  • semiology of seizure (see ILAE classification for more information)
    • focal seizures with/without impaired consciousness
    • focal to bilateral tonic-clonic seizures (FBTCS)
    • generalized seizures, most commonly tonic-clonic (GTCS)
    • unknown onset
  • number of seizures:
    • isolated seizure
    • cluster of seizures
    • acute symptomatic status epilepticus (ASSE)

Management

Detection and elimination of provoking causes

  • causal treatment of seizures – correction of metabolic disorders, management of intoxication, withdrawal of inappropriate medication, etc.

Antiseizure medication (ASM)

  • there are no clear recommendations based on trials for choosing ASMs for short-term treatment of ASSs
  • the most commonly used drugs are diazepam or clonazepam, levetiracetam, valproate, phenytoin, lacosamide
    • clonazepam is preferred for focal seizures
  • for treatment of status epilepticus, follow local protocols
  • short-term preventive treatment may be considered in selected patients

Management of seizure clusters

  • administer intravenous anticonvulsants
    • Establish intravenous (IV) access via cubital or jugular vein
  • rectal or intramuscular diazepam can be used as initial therapy
  • 1st line therapy: diazepam, midazolam
  • 2nd line therapy:
    • focal seizures: clonazepam, lacosamide
    • generalized seizures: levetiracetam, valproate, lacosamide, phenytoin
Parameter Details
Initial dosing (PO) start with 500 mg twice daily
can be rapidly titrated up;  typical increments are 500 mg every 1-2 days, depending on seizure control and tolerability
Initial dosing (IV)
  • 20-30 mg/kg + 100 mL of NS infused over 15 minutes (< 150 mg/minute)
  • SE: 30-60 mg/kg + 100 mL of NS infused over 10 minutes
Maintenance dose
 500-1500 mg twice daily, adjusted based on response, tolerance, and renal function
Notes
  • adjust dose for renal impairment
  • monitor for psychiatric symptoms such as depression or agitation
Main contraindications hypersensitivity to levetiracetam or any component of the formulation
Parameter Details
Initial dosing (PO) slow titration of 100 mg per week
Initial dosing (IV)
  • 250 mg over 5 minutes, which can be repeated to a total dose of 750-1000 mg (especially in repeated seizures)
  • SE: 15 mg/kg, administered at a rate < 50 mg/min, followed by 100mg every 6 hours
Maintenance dose
typically 300 mg/day (max dose 500mg/d) in adults divided into 2-3 doses
Notes monitor for hypotension and arrhythmias during IV administration
Contraindications
  • sinus bradycardia, sinoatrial block, second-and third-degree AV block
  • hypersensitivity to phenytoin
Parameter Details
Initial dosing (PO) start with 400-600 mg, divided into 2 doses
Initial dosing (IV)
  • repeated seizures: bolus 10-15 mg/kg, administered over 5 minutes, followed by infusion
  • SE: bolus 30 mg/kg, administered over 10 minutes (3-6 mg/kg/min), followed by infusion
  • follow-up infusion: 1-2 mg/kg /h 
    • 1200 mg+50 ml NS (1mL=24mg) IV 0.042-0.083 mL/kg/h (1-2 mg/kg/h)
Maintenance dose
  • usual daily dose: 1000-2000 mg, divided into 2-3 doses, adjusted based on clinical response and tolerance
  • target VPA levels: 300-700 µmol/L  / 50-100 µg/mL
Notes
  • monitor liver function, blood counts, and serum ammonia levels
  • be cautious of potential teratogenic effects
Contraindications
  • significant hepatic dysfunction
  • urea cycle disorders
  • porphyria
  • hypersensitivity to valproate
Parameter Details
Initial Dosing (PO) start with 50 mg twice daily
Initial Dosing (IV)
  • 200 mg +100 mL NS infused over 20-40 minutes
  • SE: 200-400 mg loading dose over 3-5 minutes, followed by a maintenance dose of 100 mg every 12 hours (then switch to PO)
Maintenance dose
100-200 mg twice daily, adjusted based on response and tolerance
Notes
  • monitor for PR interval prolongation; use caution in patients with cardiac conduction abnormalities
  • adjust dose for renal and hepatic impairment (half dose for ClCr≤30 mL/min) 
  • monitor for dizziness, ataxia
Contraindications
  • hypersensitivity to lacosamide or any component of the formulation
  • second- or third-degree AV block without an artificial pacemaker
Parameter Details
Initial Dosing (PO) start with 100-200 mg twice daily
Maintenance dose
800-1200 mg/day divided into 2 doses;  adjust dose based on response and tolerance
Notes
  • monitor for blood dyscrasias, liver function, and dermatological reactions (such as signs of Stevens-Johnson syndrome)
  • may cause dizziness and nausea
Contraindications
  • hypersensitivity to carbamazepine
  • history of bone marrow depression
  • use of MAO inhibitors within the last 14 days
Parameter Details
Initial Dosing (PO) start with 0.5 mg twice daily
Dosing (IV)
  • 1mg + 5 mL NS bolus injection over 5 minutes (max speed 0.25-0.5 mg/min)
  • 1mg + 100 mL NS  infusion over 5-10 minutes
  • continuous infusion – 5mg/20mL NS (1ml=0.25 mg) 0-2 mL/h  (0.25-0.5 mg/h)
  • maximum daily dose is 10mg
Maintenance dose
  •  1-4 mg/day in divided doses
Notes titrate dose slowly to minimize sedation and dizziness; monitor for signs of dependency and withdrawal
Contraindications significant liver disease, acute narrow-angle glaucoma, and hypersensitivity to clonazepam or benzodiazepines
ASMs therapeutic levels (values may differ in various labs)
 carbamazepine (CBZ)   17-51 µmol/L (4-12 µg/mL)
toxic level: >85 µmol/L (>20 µg/mL)
 valproate (VPA) 350-700 µmol/L (50-100 µg/mL)
toxic level:  >1040 µmol/L (>150 µg/mL)
 phenytoin (PHE) 40-80 µmol/L (10-20 µg/mL)
toxic levels: >120 µmol/L (>30 µg/mL)
 lamotrigine (LTG) 10-60 µmol/L (3-14 µg/mL)
toxic levels: >70 µmol/L (>18 µg/mL)
 levetiracetam (LEV)
35-217 µmol/L (5-25 µg/mL)
 topiramate (TPM) 10-50 µmol/L (2-10 µg/mL) 
 lacosamide (LCM) 10-60 µmol/L (2.5-15 µg/mL)

Indications for a long-term prophylactic anticonvulsant therapy

An isolated seizures, the cause has resolved (e.g., hyper/hypoglycemia, hyponatremia)

  • low risk of recurrence (<3%), ASM is not indicated

An isolated seizure or multiple seizures, the cause persists (severe stroke, TBI)

  • increased risk of recurrent seizures that could endanger the patient in the acute stage (progression of intracranial hypertension, risk of rebleeding in SAH, etc.)
  • short-term antiepileptic treatment is indicated (weeks to months); duration is influenced by imaging findings and EEG
  • If high-risk cause persists (e.g. uremia in CKD), long-term ASM can be given

An initial cluster of ASS or ASSE

  • with complete resolution of the cause, short-term ASM can be advised (<7 days)
  • with persistent cause (severe stroke, TBI), long-term ASM is recommended (months)

Two or more seizures with at least one seizure occurring > 14 days post-insult ⇒ epilepsy

  • long-term AE medication is indicated

Prognosis

  • the risk of transition from symptomatic seizures to unprovoked seizures (epilepsy) depends on the following:
    • the cause, extent, and location of lesions
      • increased risk is associated with, e.g., parenchymal hemorrhage, presence of malformations, cortical, larger ischaemic lesions, etc.
    • comorbidities (e.g., previous insults, chronic metabolic conditions)
      • premorbid and postmorbid conditions may play a role in the pathogenesis of stroke-related epilepsy (STRE)
      • the term primary STRE can be used only if no such significant condition is detected
  • prognostic tools to detect an increased risk of STRE:
  • focal seizures (especially with Todd’s hemiparesis) may pose a diagnostic challenge (Is it a new stroke or seizure? Should we initiate thrombolysis?)
  • in the case of recurrent, uniform attacks that occur despite effective secondary prevention, a therapeutic trial with ASMs is appropriate

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Acute symptomatic seizures
link: https://www.stroke-manual.com/acute-symptomatic-seizures/