1. Diagnosis and Management in the Hospital
Seizures
Diagnosis and Management in the Hospital
Melody Calla, PA-C
Physician Assistant
Department of Neurology
NorthShore University HealthSystem

2. Objectives Describe and define different types of seizures.
Identify common causes of seizures
Discuss acute hospital management of seizures

3. Definitions
Seizure
Caused by abnormal cortical neuronal activity, resulting in sudden and transient alteration of awareness, somatosensory, visual, motor, and/or behavioral changes
A symptom due to an underlying pathology (head trauma, hemorrhage/stroke, metabolic dysfunction, drug exposure, tumor) or other disorder without a clear cause

4. Definitions
Epilepsy – 2014 International League Against Epilepsy (ILAE) updated definition:
Recurrent unprovoked seizures (two or more unprovoked seizures at least 24 hours apart).
Heightened tendency toward future recurrent unprovoked seizure over the next 10 years (single seizure with abnormal EEG or MRI). Can be associated with prior stroke, CNS infection, traumatic brain injury
Diagnosis of an epilepsy syndrome

5. Definitions Status epilepticus
Continuous seizures lasting >5 minutes
At least two discrete seizures occurring without return to baseline in between
May also include persistent seizure activity despite appropriate doses of two anti-epileptic drugs (AED)
Historically, “single epileptic seizure of >30 minutes duration or a series of epileptic seizures during which function is not regained between ictal events in a 30 minute period.”

6. Incidence/Epidemiology
The cumulative life time incidence of having at least one seizure is 9%. The cumulative life time incidence of having epilepsy is 3%.
This is because 1/3 of the 9% incidence consists of children with uncomplicated febrile seizures, another 1/3 consists of patients who have only one seizure in the setting of a medical illness. The remaining 1/3 consists of patients who will be diagnosed with epilepsy.

8. Seizure types Partial (focal seizures)
Most common seizure type in adults
Caused by abnormal activity originating in a single region of the brain
Simple: no alteration of consciousness
Motor cortex: rhythmic jerking in 1 body part
Temporal lobe aura: epigastric rising, fear, déjà vu
Complex: impaired or alteration of consciousness
Automatisms: lip smacking, fumbling of fingers
Secondary generalized

9. Clues to partial onset seizures
Unilateral shaking
Head turning to 1 side (versive head turning)
Subjective aura preceding convulsion
Focal weakness after a convulsion (Todd paralysis)
can mimic an acute stroke

10. Seizure types Generalized
Involve both hemispheres of the brain at onset
Absence/petit mal – behavioral arrest, staring with unresponsiveness and automatisms, impaired awareness, but lack aura or post-ictal confusion. <5-10 seconds
Myoclonic – sudden brief jerks or twitching of limb or axial muscles, usually consciousness preserved, typical of juvenile myoclonic epilepsy (JME)
Tonic – sustained abnormal posturing of extremities
Clonic – repetitive jerking movements (rhythmic)
followed by post-ictal sedation and confusion, tongue biting, incontinence
1-3 minutes

11. Seizure mimics Physiologic events Psychiatric-based events Syncope
Migraine
TIA
Transient global amnesia
Dizziness/vertigo
Sleep disorders
Waxing and waning delirium
Intermittent movement disorders
Psychiatric-based events
Panic/anxiety attacks
Conversion, psychogenic non-epileptic seizures (PNES)
Dissociative states
Hyperventilation syndrome
Acute psychosis
malingering

12. Seizure vs. Syncope Seizure vs. Syncope Characteristic
Epileptic Seizure
Syncope
Warning/aura
Variable (<1 min)
Lightheaded feeling, sweating
Duration
1-2 min
Seconds to minutes
Position dependent No
Typically, but not always
Symptoms during episode
Variable: automatisms, confusion, aphasia, tonic-clonic movements
Loss of tone, brief tonic extension or clonic jerks (5-15%)
Altered consciousness
Common
Incontinence
Variable
Heart rate
Increased
Irregular and decreased
Symptoms after episode
Confusion, fatigue
Alert
EEG during event
Epileptiform pattern
Diffuse slowing

13. Seizure mimics TIA Duration
Negative symptoms (weakness, numbness, vision loss, aphasia, etc)
Positive symptoms during a seizure however negative symptoms can occur after

14. Seizure mimics Non-epileptic behavioral spells (Psychogenic seizures)
Description of event
Typically eyes are closed
Head nodding or shaking
Pelvic thrusting
Non-rhythmic movements in extremities
Can be different with each event
Tip of tongue biting
Can still have unresponsiveness, post-ictal confusion

15. Favoring epileptic seizures
Aura
Brief duration (1-2 min)
Post-ictal confusion
Abnormal posturing
Amnesia for the event
Incontinence
Events arising from sleep
Self-injury (lateral tongue biting)
Eyes open at the event onset

16. Evaluation
Determine whether the episode of loss of consciousness was a seizure or other event.
History
Prior seizures (including febrile), family history of epilepsy
Head trauma
Cerebrovascular disease, Cardiovascular disease, Diabetes
Cancer
Substance abuse
Intracranial infection
Recent travel, occupation
Congenital brain malformation, cerebral degeneration

17. Provoked seizures Condition Specific Cause Metabolic disturbance
Hyponatremia, hypo- or hypercalcemia, hypo- or hyperglycemia, uremia
Drug intoxication
Cocaine, phencyclidine, methamphetamines
Drug withdrawal
EtOH withdrawal, benzo withdrawal, barb withdrawal, baclofen withdrawal
Medication-induced lowered seizure threshold
Bupropion, cefepime, ciprofloxacin, clozapine, cyclosporine, imipenem, isoniazid, tacrolimus, theophylline, TCAs, tramadol
Infection
Encephalitis, meningitis
Vasculopathy
Eclampsia, hypertensive encephalopathy, PRES syndrome

18. Evaluation during a seizure
Observe as much as possible and be aware of duration of event
Level of consciousness
Responsive, altered/confused, unresponsive
Motor movements (head, arms, legs).
Right, left, or bilateral?
Rhythmic jerking, twitching, stiffening, posturing
Eyes open, deviated towards one direction, or closed, eyelid flickering
Vitals, incontinence

19. Evaluation after a seizure
ABCs
Vitals including O2 sats, blood glucose. Suction if need
Level of consciousness
Cognition/orientation, behavioral changes, weakness, confusion, speech/language changes
Any injury (tongue biting, trauma, incontinence)
Motor function

20. Labs Glucose Electrolytes Alcohol level Urine toxicology screen EKG
Both hypo- and hyperglycemia can precipitate seizures
Electrolytes
Hyponatremia, hypomagnesium, hypocalcemia
Alcohol level
Seizures often associated with withdrawal, usually within 48 hours from last drink
Can have seizures from overuse
Urine toxicology screen
Amphetamines, cocaine, PCP
Sedatives (i.e., benzodiazepines) can cause seizures after withdrawal from chronic use
Not always routine, mostly obtain based on history. Inadequate evidence to support or refute.
EKG

21. Labs
Prolactin
Limited role as a diagnostic test for epileptic seizures
May rise shortly after generalized tonic-clonic seizures and sometimes focal seizures
Low sensitivity, so a normal may be seen in a real seizure as well as non-epileptic event

22. Labs Lumbar puncture for cerebrospinal fluid (CSF)
Not typically routine unless presentation supports acute infectious process involving central nervous system or cancer history (in which carcinomatous meningitis or leptomeningeal disease is suspected).
A prolonged seizure itself can cause a pleocytosis in CSF making results misleading.

23. Neuroimaging
In the acute setting, CT head without contrast to evaluate for bleed and/or mass
MRI brain with and without gadolinium is ideal
Tumor, vascular malformation, posttraumatic changes, mesial temporal sclerosis, cortical malformations
Include “seizure protocol” in comment section of the order so thin cuts of temporal lobes can be obtained.

24. Electroencephalogram (EEG)
If possible, obtain as close as possible to seizure activity
Normal EEG does not exclude presence of a seizure disorder.
helps support the evidence.
May consider treatment with an abnormal EEG (epileptiform discharges) after a single seizure
Presence of epileptiform abnormality does not always indicate seizure disorder
take into context of the patient and current situation
Medication effects, renal failure, or other acute encephalopathy

25. Electroencephalogram (EEG)
Video EEG
Useful in identifying or classifying the seizure disorder or spell (non-epileptic)

26. Treatment of seizures Benzodiazepines
Lorazepam 0.1 mg/kg IV given at 2 mg/min
longer half life than Diazepam
Side effects - respiratory/cardiovascular depression, somnolence, which can confuse resolution of seizure/post-ictal phase vs persistent seizures.

27. Selection of AEDs
No single AED is recommended for the initial treatment of epilepsy.
~50% will respond to the 1st AED
Factors to consider:
Epilepsy syndrome
Age
Sex
Comorbidities
Drug side effects
Cost

28. Antiepileptic Drugs Broad spectrum Lamotrigine Levetiracetam
Topiramate
Valproic acid
Zonisamide
Clobazam
Felbamate
Perampanel
Rufinamide
Narrow spectrum
Carbamazepine
Gabapentin
Oxcarbazepine
Phenobarbital
Phenytoin
Pregabalin
Eslicarbazepine
Ezogabine
Lacosamide
Primidone
Tiagabine
Vigabatrin

29. Treatment of Seizures Phenytoin/Fosphenytoin
Fosphenytoin is prodrug to Phenytoin, lacks a diluent that Phenytoin has in its formulation.
At NorthShore, IV Phenytoin not available
Dosing is the same: load mg/kg.
Obtain post-load Dilantin level ~2 hours, helps in maintenance dosing (typically 5 mg/kg/day).
When given IV, maintenance dose every 8 hours due to short half-life
Oral dosing: Phenytoin ER caps (100 mg, 200 mg, 30 mg), chewable 50 mg, suspension
Side effects: hypotension, bradycardia, cardiac arrhythmia , ataxia (toxic), nystagmus, skin rash, gingival hyperplasia, vitamin D deficiency, purple glove syndrome (IV)

30. Treatment of Seizures Fosphenytoin/Phenytoin (continued)
Protein binding
Drug levels may need to be adjusted in hypoalbuminemia
Adjusted concentration = measured total concentration divided by [(0.2 x albumin) + 0.1].
Metabolism – CYP450 family
Enhance anticoagulant effects of Vitamin K antagonists (Warfarin). Conversely, vitamin K antagonists increase serum concentration of Phenytoin
Decrease serum concentration of Valproic Acid (Depakote)

31. Treatment of seizures Levetiracetam (Keppra)
Loading dose: mg IV
Maintenance dose: starts at 500 mg twice a day
Maximum 3000 mg daily total. Doses beyond can be used but no evidence of additional benefit.
Formulation: 250 mg, 500 mg, 750 mg, 1000 mg tablets, suspension, IV.
Cannot be crushed

32. Treatment of seizures Levetiracetam (continued)
Dose adjustment in renal impairment, based on Creatinine Clearance
Dose 500 mg-1000 mg every 24 hours in patients with end-stage renal dialysis requiring hemodialysis (HD) or peritoneal dialysis (PD).
Twice daily dosing in patients receiving continuous renal replacement therapy (CRRT)

33. Treatment of seizures Levetiracetam (continued)
Drug level commonly used to monitor compliance and in patients with renal impairment
Side effects: behavioral changes (aggression, anger, anxiety, irritability), fatigue

34. Treatment of seizures Valproic Acid (Depakote, Depakene, Depacon)
Loading dose: mg/kg IV
Maintenance dose: mg/kg/day, can be increased by 5-10 mg/kg/day at weekly intervals (or quicker if needed in hospital setting)
Formulation: Regular, delayed or extended release in 125 mg, 250 mg, 500 mg capsules, tablets, suspension, sprinkles
Metabolism: liver
Not ideal for patients with hepatic impairment
Side effects: tremor, nausea, diarrhea, thrombocytopenia (dose related), weight gain

35. Treatment of seizures Phenobarbital Loading dose: 20 mg/kg IV
Maintenance dose: 1-5 mg/kg/day, 12 hours after loading dose
Metabolism: liver via CYP system
Side effects: hypotension, respiratory depression, sedation
Half life is ~79 hours, thus obtaining a “therapeutic level” can take several days

36. Treatment considerations
Enzyme-inducers (Phenytoin, Oxcarbazepine, Phenobarbital) can interact with other liver-metabolized drugs (including BCPs) and can increase risk of osteoporosis and hypercholesterolemia.
Valproic Acid avoid as a 1st-line drug in women of childbearing age due to risk of congenital and cognitive abnormalities in offspring.
Lamotrigine – consider in women, older patients, depression or other mood disorders
Topiramate and Zonisamide – can be used for both generalized and partial epilepsy; assoc. with weight loss; risk of kidney stones
Levetiracetam and Gabapentin – useful in the elderly since it doesn’t interact with the other medications they may be on.

37. Brain tumors – primary and metastatic
When presenting with a seizure, use of non-enzyme inducing AED is ideal (Levetiracetam) to avoid potential drug interactions with chemotherapies.
No history of seizure and no plan for neurosurgical procedure: N0 prophylaxis is recommended.
No history of seizure with neurosurgical resection: short duration of perioperative prophylaxis is recommended as long as patient remains seizure free.

38. Driving https://www.epilepsy.com/driving-laws
In IL, physicians are not required to report patients with epilepsy to the state
However, physicians may report when patients act against medical advice
There is no set seizure-free period prior to resumption of driving
6 months is a common time frame
Other variables may be associated alteration of awareness. Simple partial seizures may have shorter time frame (3 months)
Patients should be aware of the responsibility should an accident occur during the restrictive period

39. When to Treat 2 or more unprovoked seizures
After a single seizure with ≥1 risk factors:
>65 yrs old
History of significant head trauma
partial seizure
Post-ictal Todd paralysis
focal finding on EEG or brain
If both MRI and EEG are normal after a single unprovoked seizure, 2 yr recurrence risk ~30-40%
Early treatment is justified in those for whom any seizure recurrence would have significant consequences related to driving, working, and general safety.

40. Conclusions
Seizures is a common neurologic condition presenting to the Emergency Department
Recognition of specific clinical characteristics and risk factors help to differentiate between seizure and other neurologic disorders.
Prompt evaluation of a seizure event and treatment helps improve patient outcomes.