Chronic Post-Stroke Seizures

Excessive Neuronal Activity Following Ischemic Neuronal Injury: The Identification i of Acute and Chronic Post-Stroke Seizures David E. Burdette, M.D. Assistant Professor of Neurology Wayne State University School of Medicine Director EEG Laboratory, Henry Ford Hospital

Pti Patient t1 67-year-old with stroke and change in mental status t

Si Seizure versus Eil Epilepsy Si Seizure: bif brief, uncontrolled llddischarge of fthe nerve cells of the brain Incidence: approximately 80/100,000 000 per year Occurs in 8-10% of people in their lifetime (1/3 febrile) Epilepsy: a tendency toward recurrent, unprovoked seizures Incidence: approximately 45/100,000 000 per year Occurs in 3-4% of people in their lifetime About 1 in 200 people have epilepsy

Epilepsy Incidence: Rochester, Minnesota 1935 to 1984 Male 0,000 Pers son-years 200 150 100 Female Total Inciden nce per 10 50 0 0 20 40 60 80 Age (years) Hauser WA et al. Epilepsia. 1993;34:453 468. Hauser WA, et al. Epilepsia. 1993;34:453-468. Adapted with permission of the journal Epilepsia.

Seizure Types Nonepileptic Epileptic Syncope Migraine Psychogenic Toxic Metabolic Cerebrovascular Generalized Tonic-clonic Tonic Clonic Absence Myoclonic Atonic Partial Simple Complex Convulsive Secondarily Nonconvulsive generalized International League Against Epilepsy, Commission on Classification and Terminology. Epilepsia. 1981;22:489-501.

Seizure Types Stroke-associated seizures Nonepileptic Epileptic Syncope Migraine Psychogenic Toxic Metabolic Cerebrovascular Generalized Tonic-clonic Tonic Clonic Absence Myoclonic Atonic Partial Simple Complex Convulsive Secondarily Nonconvulsive generalized International League Against Epilepsy, Commission on Classification and Terminology. Epilepsia. 1981;22:489-501.

Neuronal Circuits

CNS Seizure Burdette

Seizure Precipitants Acute symptomatic seizures Excessive excitation Metabolic/electrolytic imbalance Stimulant/proconvulsant intoxication Inadequate inhibition Metabolic/electrolytic imbalance Sedative/ethanol withdrawal

Post-Stroke Seizures Early onset (within first 2 weeks) Majority within the first 24 hours Due to focal cerebral irritability Increased extracellular potassium Excessive excitotoxic neurotransmitter release Lt Late onset t(2 weeks or later) lt Gliosis formation Greater risk of subsequent epilepsy Bladin C, et al. Arch Neurol. 2000;57:1617-1622 1622

Post-Stroke Seizures Ischemic stroke Early-onset seizures 3-5% of patients t 30-50% of all seizures are within first 24 hours Late-onset seizures 2-5% of patients 40-60% develop epilepsy Bladin C, et al. Arch Neurol. 2000;57:1617-1622 1622

Post-Stroke Seizures Hemorrhagic stroke Early-onset seizures 7-10% of patients >50% of all seizures are within first 24 hours Late-onset seizures 2-5% of patients 80-100% develop epilepsy Bladin C, et al. Arch Neurol. 2000;57:1617-1622 1622

Acute Seizures after Stroke ceeg in 109 consecutive patients 46 with acute hemispheric stroke 63 with primary intracerebral hemorrhage 1997 2001 Indications for ceeg Any ICH All received prophylactic phenytoin (PHT) Ischemic stroke with GCS<12 or NIHSS >8 Prophylactic PHT if required surgery or ventriculostomy Vespa, et al. Neurology 2003;60:1441-1446.

Acute Seizures after Stroke Principal findings regarding acute post-stroke seizures Occur more often with ICH (27.8%) than ischemic stroke (6%) Occur in lobar and subcortical ICH Associated with worsening of NIHSS scores with ICH Associated with progressive midline shift after ICH Independent of size of hemorrhage Including nonconvulsive seizures Trend toward worse outcome after ICH Rate of nonconvulsive seizures 4 times the rate of clinical ones Vespa, et al. Neurology 2003;60:1441-1446.

Effect of Seizures on Midline Shift Vespa, et al. Neurology 2003;60:1441-1446.

Electrographic Seizures in ceeg 603 consecutive patients 570 patients (95%) for unexplained change in mental status June 1996 December 2002 Indications for ceeg Unexplained decrease in level of consciousness Titration of continuous IV AED in refractory SE Titration of IV pentobarbital in increased ICP Claassen, et al. Neurology 2004;62:1743-8.

INSERT TABLE 2 Claassen, et al. Neurology 2004;62:1743-8.

PEDs table 4 Claassen, et al. Neurology 62:1743-8.

Terminology: Periodic Epileptiform Activity Periodic epileptiform discharges (PEDs) Lateralized (PLEDs) Lateralized, occurring independently overeach hemisphere (BIPLEDs) Generalized (GPEDs) Stimulus-induced rhythmic periodic or ictal Stimulus induced rhythmic, periodic, or ictal discharges (SIRPIDs)

Normal Awake

Periodic Lateralized Epileptiform Discharges (PLEDs) T.C. 1.0 sec H.F.F. 70 Hz

Bilateral Independent Periodic Epileptiform Discharges (BIPLEDs)

Stimulus-Induced Rhythmic, Periodic, or Ictal Discharges (SIRPIDs) - Unstimulated

SIRPIDs - Stimulated Right frontal artifact from pneumatic chest percussion device

Indications for ceeg: Spells of Unclear Etiology Consider ceeg for Paroxysmal or repetitive movements Subtle twitching, nystagmus, unexpplained eye deviation, chewing movements Autonomic spells (e.g. brady/tachycardia) Hirsch. J Clin Neurophysiology. 21(5):332-340.

Treatment of (Post-Stroke) Seizures Increase inhibition Barbiturates Benzodiazepines Valproate Decrease excitation Felbamate Topiramate Decrease rapidity of neuronal firing Sdi Sodium channel modulators dlt Fast v slow inactivated Synaptic vesicle releasing protein Presynaptic calcium α2δ binding site

IV I.V. AEDO Options Benzodiazepines i Diazepam Lorazepam Phenytoin Fosphenytoin Lacosamide Levetiracetam Phenobarbital Valproate sodium

Common Loading Doses for Parenteral AEDs in Adults Drug Phenytoin Phenobarbital bit Valproate Diazepam Lorazepam Levetiracetam Lacosamide Loading Dose 15-20 mg/kg 1 15-20 mg/kg 2 20 mg/kg 3 5-10 mg 1-4 mg 30-50 mg/kg g 3 5-10 mg/kg 3 1 No faster than 50 mg/min 2 No faster than 100 mg/min; if not mechanically ventilated, no more than 10 mg/kg 3 No approved loading dose

Patient 1

Pti Patient t1 EEG diagnosis i partial status t epilepticus Resolved with phenytoin and levetiracetam Clinical i l diagnosis i Change in mental status due to Acute left posterior cerebral artery stroke Residual mild dysarthria and forgetfulness Partial status epilepticus resolved

Patient 2 (stimulated)

Patient 2 (unstimulated)

Pti Patient t2 EEG diagnosis triphasic waves Most commonly seen in the setting of hepatic or renal dysfunction Clinical diagnoses Acute subcortical stroke Change in mental status due to urinary tract infection Resolved with antibiotics

Detection of Subtle Seizures Most common application for ceeg Consider ceeg for Fluctuating mental status Unexplained change in mental status Acute supratentorial injury with change in mental status Following convulsive status epilepticus PEDs on routine EEG Hirsch. J Clin Neurophysiology. 21(5):332-340.

Burdette

Use of Loading Dose Administer loading dose to obtain target serum concentrations rapidly Useful lin seizure emergencies

Determining Loading Dose Loading Dose (mg) = Weight (kg) x V D (L/kg) x Change in concentration V D = volume of distribution Change in concentration = Desired AED level - Current AED level

Volumes of Distribution (V D ) for Parenteral AEDs* Drug Phenytoin Phenobarbital Valproate Diazepam Lorazepam Levetiracetam t Lacosamide Mean V D (L/kg) O.75 0.6 0.2 0.8-2.0 1.0-1.31.3 0507 0.5-0.7 07 0.7 0.6 * Levy RH, et al. Antiepileptic Drugs. 1995.

AEDs CNS Seizure