Seizures

Definitions <NEJM 2003:349:1257)

• Seizure - abnormal, paroxysmal, excessive discharge of CNS neurons; occurs in

5-10% of the population; clinical manifestations can range from dramatic to subtle

• Epilepsy - recurrent seizures due to an underlying cause; 0.5-1.0% of population

• Generalized seizures (involves brain diffusely)

Tonic-clonic (grand mal): tonic phase (10-20 sec) with contraction of muscles (causing expiratory moan, cyanosis, pooling of secretions, tongue biting) -* clonic phase ( 30 sec) with intermittent relaxing and tensing of muscles Absence (petit mal): transient lapse of consciousness w o loss of postural tone Myoclonic (infantile spasms & juvenile myoclonic epilepsy): sudden, brief contraction

• Partial or focal seizures (involves discrete areas, implies a focal, structural lesion)

Simple: without impairment of consciousness; may be motor, sensory, or autonomic Complex: with impairment of consciousness = automatisms or psychogenic features Partial with secondary generalization: starts focal, becomes diffuse

• Syncope: lacks true aura (although Pi may describe feeling unwell w diaphoresis, nausea.

and tunneling of vision), motor manifestations <30 sec (convulsive activity for <10 sec may occur with transient cerebral hypoperfusion), and w o postictal disorientation, muscle soreness, or sleepiness; skin pallor & clamminess support syncope

• Psychogenic seizure: may see side-to-side head turning, asymmetric large amplitude limb movements, diffuse twitching w o LOC. and crying talking during event

• Other: metabolic disorders (eg. alcoholic blackouts, hypoglycemia); migraines;TlAs;

narcolepsy; nonepileptic myoclonus Etiologies

• Alcohol withdrawal, illicit drugs, meds (eg. p-lactams. meperidine. CsA. antidep..

clozapine)

• Brain tumor or penetrating trauma

• Cerebrovascular disease, including subdural hematomas, hypertensive encephalopathy

• Degenerative disorders of the CNS (eg. Alzheimer's)

• Electrolyte (hyponatremia) & other metabolic (eg. uremia, liver failure, hypoglycemia) Clinical manifestations

• Aura (sec to mins): premonition consisting of abnormal smells tastes, unusual behavior.

oral or appendicular automatisms i

• Ictal period (sec to mins): tonic and or clonic movements of head. eyes, trunk or extrem

• Postictal period (mins to h): slowly resolving period of confusion, disorientation, and lethargy. May be accompanied by focal neurological deficits ("Todd's paralysis").

• Status epilepticus: continuous tonic-clonic seizure >30 mins. or repeated seizures such that there is no resolution of postictal periods. Complications include neuronal death, rhabdomyolysis. and lactic acidosis. I

• Nonconvulsive status epilepticus alteration of awareness (ranging from confusion to coma) w o motor manifestations. Dx with EEG. Clinical evaluation

• Seizure: patient usually w o recollection, must talk to witnesses unusual behavior before seizure (ie. an aura)

type & pattern of abnl movements, ind. head turning & eye deviation (gaze preference away from seizure focus) loss of responsiveness

• HPI: recent illnesses fevers, head trauma

• PMH: prior seizures or © FHx. prior meningitis encephalitis, prior stroke or head trauma

• Medications, alcohol, and illicit drug use

• General physical exam should include the skin, looking for neuroectodermal disorders

(eg. neurofibromatosis, tuberous sclerosis) that are associated with seizures

• Neurological exam should look for focal abnormalities — underlying structural abnormality

^ Diagnostic studies

• Laboratory: full electrolytes. BUN, Cr. glc, LFTs. tox screen, medication levels

frequent seizures: can confirm by demonstrating repetitive rhythmic activity (nb.

generalized seizures will always have abnormal EEG; partial seizures may not) infrequent seizures: may show interictal epileptiform activity (eg, spikes or sharp waves), but such patterns seen in up to 2% of normal population sleep deprivation t dx yield of EEG; video monitoring may help w psychogenic seizures

• MRI to r o structural abnormalities; t Se w fine coronal cuts of frontal & temporal lobes

• Lumbar puncture (after ruling out space-occupying lesion): if suspect meningitis or encephalitis and in all HIV ® patients

Treatment (NEJM 2001:344:1145: lancet 2006:367 1087 & 2007:349:1000.1016)

• Treat any underlying causes, including CNS infections, intoxication or withdrawal, etc.

• Antiepileptic drug (AED) therapy is usually reserved for Pts w underlying structural abnormality or an idiopathic seizure plus (1) status epilepticus on presentation. (2) focal neurologic exam. (3) postictal Todd's paralysis, or (4) abnormal EEG

• For Pts w infrequent seizures, earty (vs. delayed) intervention w AED t time to seizure recurrence, but has no effect on long-term seizure-free status (lance1 2005:365:2007)

• Generalized tonic-clonic: valproic acid, phenytoin. topiramate. lamotrigine

• Partial (w/ or w/o 2° generalization): carbamazepine. oxcarbazepine. lamotrigine.

phenytoin. valproic acid

• Absence: ethosuximide. valproic acid

• Secondary agents: leviteracitam. gabapentin. clonazepam, phenobarbital

• Introduce gradually, monitor carefully

• May consider withdrawal if seizure-free (typically for at least 1 y) and normal EEG

• Individual state laws mandate seizure-free duration before being allowed to drive

Antiepileptic Drugs and Side Effects

Medication

Avg daily dose

Side effects

Neurologic Systemic

Phenytoin

300-400 mg

Gum hyperplasia, i Ca. î K

Carbamazepine

600-1800 mg

Dizziness Ataxia

Aplastic anemia Leukopenia Hepatotoxicity Hyponatremia

Valproic acid

750-2000 mg

Diplopia Confusion

Hepatotoxicity. î NH} Thrombocytopenia

Phenobarbital

60-180 mg

Drowsiness

Rash

Ethosuximide

750-1250 mg

Bone marrow suppression

Gabapentin

900-2400 mg

Gl upset

Leviteracitam

1500-3000 mg

Drowsiness Emotional lability

GI upset (rare)

(JAMA 2004:291:60S. 615)

(JAMA 2004:291:60S. 615)

Status epilepticus (consult neurology)

• Place Pt in semiprone position to i risk of aspiration

• Oral airway or. if prolonged, endotracheal intubation

• IV access, start normal saline infusion

• STAT labs including glc. Na. Ca. serum & urine toxicology screen, anticonvulsant levels

• Thiamine (100 mg IV) prior to dextrose to prevent exacerb. of Wernicke's encephalopathy

• Na or Ca repletion as needed

Treatment of Status Epilepticus (proceed to next step If seizures continue)

Step Antiepileptic Dosing regimen Typical adult dose

1

Lorazepam or 0.1 mg kg at 2 mg min Diazepam 0.2 mg kg at 5 mg min

Successive 2-4 mg IV pushes Successive 5-10 mg IV pushes

Lorazepam marginally slower onset of action (3 vs. 2 min) but at least as efficacious (success 65%) & longer duration of effect (12-24 h vs. 15-30 min)

2

Phenytoin or 20 mg kg at 50 mg min Fosphenytoin 20 mg PE kg at 150 mg min + 5-10 mg kg if still seizing

1.0-1.5 g IV over 20 min 1.0-1.5 g PE IV over 5-10 min • 500 mg IV if still seizing

Subsequent steps typically mandate intubation, EEC monitoring, and ICU admission

3

Phenobarbital 20 mg kg at 50-75 mg min ♦ 5-10 mg kg if still seizing

1.0-1.5 g IV over 30 min ♦ 500 g IV if still seizing

4

General anesthesia with midazolam, pentobarbital, or propofol

(JAMA 1983:249.1452; NiJM 1998.338:970 & 339:792)

(JAMA 1983:249.1452; NiJM 1998.338:970 & 339:792)

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