Chronic Post-Stroke Seizures

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1 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

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

3 Pti Patient t2 68-year-old with stroke and change in mental status t

4 Si Seizure versus Eil Epilepsy Si Seizure: bif brief, uncontrolled llddischarge of fthe nerve cells of the brain Incidence: approximately 80/100, 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, per year Occurs in 3-4% of people in their lifetime About 1 in 200 people have epilepsy

5 Epilepsy Incidence: Rochester, Minnesota 1935 to 1984 Male 0,000 Pers son-years Female Total Inciden nce per Age (years) Hauser WA et al. Epilepsia. 1993;34: Hauser WA, et al. Epilepsia. 1993;34: Adapted with permission of the journal Epilepsia.

6 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:

7 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:

8 Neuronal Circuits

9 CNS Seizure Burdette

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

11 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:

12 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:

13 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 % develop epilepsy Bladin C, et al. Arch Neurol. 2000;57:

14 Acute Seizures after Stroke ceeg in 109 consecutive patients 46 with acute hemispheric stroke 63 with primary intracerebral hemorrhage 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:

15 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:

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

17 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:

18 INSERT TABLE 2 Claassen, et al. Neurology 2004;62:

19 PEDs table 4 Claassen, et al. Neurology 62:

20 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)

21 Normal Awake

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

23 Bilateral Independent Periodic Epileptiform Discharges (BIPLEDs)

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

25 SIRPIDs - Stimulated Right frontal artifact from pneumatic chest percussion device

26 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):

27 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

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

29 Common Loading Doses for Parenteral AEDs in Adults Drug Phenytoin Phenobarbital bit Valproate Diazepam Lorazepam Levetiracetam Lacosamide Loading Dose mg/kg mg/kg 2 20 mg/kg mg 1-4 mg mg/kg g 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

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

31 Patient 1

32 Patient 1

33 Patient 1

34 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

35 Pti Patient t2 68-year-old with stroke and change in mental status t

36 Patient 2 (stimulated)

37 Patient 2 (unstimulated)

38 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

39 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):

40 Burdette

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

42 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

43 Volumes of Distribution (V D ) for Parenteral AEDs* Drug Phenytoin Phenobarbital Valproate Diazepam Lorazepam Levetiracetam t Lacosamide Mean V D (L/kg) O * Levy RH, et al. Antiepileptic Drugs

44 AEDs CNS Seizure

δ > Table 2: Prognostic index for recurrence of seizures after remission of epilepsy for patients taking only one antiepileptic drug (AED) Risk of seizure recurrence by two years (%) Period free from

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