New Onset Seizure

VERSION: 1.1
CREATED: January 13, 2026
REVISED: January 13, 2026
STATUS: Revised per physician feedback

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DIAGNOSIS: New Onset Seizure

ICD-10: R56.9 (Unspecified convulsions), G40.909 (Epilepsy, unspecified, not intractable, without status epilepticus), G40.901 (Epilepsy, unspecified, not intractable, with status epilepticus), G40.309 (Generalized idiopathic epilepsy, not intractable, without status epilepticus), G40.409 (Other generalized epilepsy, not intractable, without status epilepticus), R56.1 (Post-traumatic seizures)

SYNONYMS: New onset seizure, first seizure, single seizure, first-time seizure, unprovoked seizure, initial seizure, new-onset epilepsy, convulsion, fit, spell, NOS, new seizure, de novo seizure, acute symptomatic seizure, provoked seizure, tonic-clonic seizure, grand mal seizure, focal seizure, partial seizure, generalized seizure, seizure NOS, first-time convulsion

SCOPE: Initial evaluation and management of first-time unprovoked seizure or first presentation of seizure activity in adults. Covers immediate stabilization, diagnostic workup to identify etiology, acute treatment, and framework for anti-seizure medication (ASM) initiation. Excludes status epilepticus (see "Status Epilepticus" template), pediatric seizures, febrile seizures, and known epilepsy with breakthrough seizures.

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PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting

═══════════════════════════════════════════════════════════════ SECTION A: ACTION ITEMS ═══════════════════════════════════════════════════════════════

1. LABORATORY WORKUP

1A. Essential/Core Labs

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
Point-of-care glucose (CPT 82962)	STAT	STAT	-	STAT	Hypoglycemia is immediately reversible cause	>70 mg/dL
CBC with differential (CPT 85025)	STAT	STAT	ROUTINE	STAT	Infection screen, baseline before ASMs	Normal
CMP (BMP + LFTs) (CPT 80053)	STAT	STAT	ROUTINE	STAT	Electrolyte abnormalities (Na, Ca, Mg, glucose), renal/hepatic function for ASM dosing	Normal
Magnesium (CPT 83735)	STAT	STAT	ROUTINE	STAT	Hypomagnesemia lowers seizure threshold	>1.8 mg/dL
Calcium, ionized (CPT 82330)	STAT	STAT	ROUTINE	STAT	Hypocalcemia can cause seizures	Normal (ionized 4.5-5.3 mg/dL)
Urine drug screen (CPT 80307)	STAT	STAT	ROUTINE	STAT	Illicit drugs (cocaine, amphetamines) and withdrawal states	Negative
Blood alcohol level (CPT 80320)	STAT	STAT	-	STAT	Alcohol intoxication or withdrawal	Correlate with history
Urinalysis (CPT 81003)	STAT	STAT	ROUTINE	STAT	UTI can provoke seizures (especially elderly)	Negative
Prolactin level	STAT	-	-	STAT	Elevated if drawn within 10-20 min of event; helps distinguish seizure from non-epileptic event	Elevated 2-3× baseline (if drawn <20 min)
Phosphorus (CPT 84100)	STAT	STAT	ROUTINE	STAT	Hypophosphatemia lowers seizure threshold (especially alcohol withdrawal)	>2.5 mg/dL

1B. Extended Workup (Second-line)

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
TSH (CPT 84443)	URGENT	ROUTINE	ROUTINE	URGENT	Thyroid dysfunction can affect seizure threshold	Normal
Ammonia (CPT 82140)	URGENT	ROUTINE	-	URGENT	Hepatic encephalopathy, urea cycle disorders	Normal (<35 μmol/L)
Troponin (CPT 84484)	URGENT	ROUTINE	-	URGENT	Cardiac ischemia as cause or consequence	Negative
ECG (CPT 93000)	URGENT	ROUTINE	ROUTINE	URGENT	Arrhythmia, prolonged QTc (some ASMs), Brugada	Normal
Lactate (CPT 83605)	URGENT	ROUTINE	-	URGENT	Elevated post-ictal; also metabolic acidosis	Mild elevation acceptable post-ictal
Blood gas (ABG or VBG) (CPT 82803)	URGENT	ROUTINE	-	URGENT	Acidosis, hypoxia	Normal or mild post-ictal acidosis
Serum osmolality (CPT 83930)	URGENT	ROUTINE	-	URGENT	Hypo/hyperosmolar states	280-295 mOsm/kg
Pregnancy test (urine or serum β-hCG)	STAT	STAT	ROUTINE	STAT	Eclampsia; affects imaging and ASM choice	Negative (or explains eclampsia if positive)
B12 level (CPT 82607)	-	ROUTINE	ROUTINE	-	Deficiency associated with seizures	Normal (>300 pg/mL)
Folate level (CPT 82746)	-	ROUTINE	ROUTINE	-	Deficiency can lower threshold; important for women of childbearing potential	Normal

1C. Rare/Specialized (Refractory or Atypical)

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
Serum/urine toxicology (expanded panel)	URGENT	EXT	EXT	URGENT	Synthetic drugs, medications not on standard screen	Negative
Heavy metals (lead, mercury)	-	EXT	EXT	-	Occupational exposure, pica	Normal
Ceruloplasmin, serum copper	-	EXT	EXT	-	Wilson disease (young patients)	Normal
HIV (CPT 87389)	-	ROUTINE	ROUTINE	-	HIV-associated CNS disease	Negative
RPR/VDRL (CPT 86592)	-	ROUTINE	ROUTINE	-	Neurosyphilis	Negative
Autoimmune encephalitis panel (serum)	-	EXT	EXT	-	Anti-NMDAR, LGI1, CASPR2, GABA-B if clinical suspicion	Negative
Paraneoplastic panel (serum)	-	EXT	EXT	-	Subacute onset, smoking, weight loss	Negative
Porphyrins (urine/serum)	-	EXT	EXT	-	Acute intermittent porphyria	Normal
Genetic epilepsy panel	-	-	EXT	-	Young onset, family history, refractory	Variable

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2. DIAGNOSTIC IMAGING & STUDIES

2A. Essential/First-line

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
CT head without contrast (CPT 70450)	STAT	STAT	-	STAT	Immediate in ED	Mass, hemorrhage, stroke, calcification, hydrocephalus	Pregnancy (relative - benefit usually outweighs risk)
MRI brain with and without contrast (epilepsy protocol)* (CPT 70553)	URGENT	URGENT	ROUTINE	URGENT	Within 24-48h if inpatient; within 2 weeks if outpatient	Tumor, mesial temporal sclerosis, cortical dysplasia, encephalitis, stroke, vascular malformation	GFR <30, gadolinium allergy, pacemaker
EEG (routine) (CPT 95816)	URGENT	URGENT	ROUTINE	URGENT	Within 24h if possible; ideally within 24-48h of seizure	Epileptiform discharges (spikes, sharp waves), focal slowing	None significant

Epilepsy MRI protocol should include: thin-cut coronal T2/FLAIR through hippocampi, 3D T1 volumetric, T2, SWI, DWI, post-contrast T1

IMPORTANT: CT head is useful for acute exclusion of hemorrhage, large mass, or hydrocephalus but is NOT sufficient to identify seizure etiology. MRI brain with epilepsy protocol remains the gold standard and should be obtained in all patients with new onset seizure.

2B. Extended

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
Continuous EEG (cEEG) monitoring (CPT 95700)	-	URGENT	-	URGENT	If altered mental status persists, suspected non-convulsive status	Non-convulsive seizures, non-convulsive status epilepticus	None significant
Prolonged ambulatory EEG (24-72h)	-	-	ROUTINE	-	Outpatient if routine EEG non-diagnostic	Capture interictal or ictal activity	None significant
Video-EEG monitoring	-	ROUTINE	ROUTINE	-	If diagnosis uncertain (vs. psychogenic)	Correlate clinical events with EEG	None significant
MRA/MRV brain	-	ROUTINE	ROUTINE	-	If vascular etiology suspected	AVM, aneurysm, venous thrombosis	Same as MRI
CT angiography head (CPT 70496)	URGENT	URGENT	-	URGENT	If MRA unavailable and vascular cause suspected	Vascular malformation, aneurysm	Contrast allergy, renal insufficiency
Echocardiogram (CPT 93306)	-	ROUTINE	ROUTINE	-	If embolic stroke suspected as cause	Thrombus, PFO, vegetation	None significant
Chest X-ray (CPT 71046)	URGENT	ROUTINE	-	URGENT	Aspiration risk post-ictal, lung cancer screening if paraneoplastic suspected	Clear lungs or mass	None significant

2C. Rare/Specialized

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
PET-CT brain (interictal FDG)	-	EXT	EXT	-	Epilepsy surgery workup	Focal hypometabolism	Pregnancy, uncontrolled diabetes
SPECT (ictal/interictal)	-	EXT	EXT	-	Epilepsy surgery workup	Ictal hyperperfusion	Requires seizure capture
MEG (magnetoencephalography)	-	-	EXT	-	Epilepsy surgery workup	Localize epileptogenic focus	Metallic implants
Neuropsychological testing	-	-	EXT	-	Pre-surgical evaluation, cognitive concerns	Lateralizing deficits	Patient cooperation
Wada test (intracarotid amobarbital)	-	-	EXT	-	Pre-surgical language/memory lateralization	Language and memory dominance	Contrast allergy, vascular anomaly

LUMBAR PUNCTURE (CPT 62270)

Indication: Suspected CNS infection (meningitis, encephalitis), autoimmune encephalitis, carcinomatous meningitis, or atypical presentation with fever/immunocompromise

Timing: URGENT if infection suspected; ROUTINE if autoimmune workup

Volume Required: 15-20 mL (standard diagnostic); 20-30 mL if malignancy suspected

Study	ED	HOSP	OPD	Rationale	Target Finding
Opening pressure	URGENT	ROUTINE	ROUTINE	Elevated ICP, mass effect	10-20 cm H2O
Cell count (tubes 1 and 4) (CPT 89051)	URGENT	ROUTINE	ROUTINE	Infection, inflammation	WBC <5; RBC 0
Protein (CPT 84157)	URGENT	ROUTINE	ROUTINE	Elevated in infection, inflammation	15-45 mg/dL
Glucose with serum glucose (CPT 82945)	URGENT	ROUTINE	ROUTINE	Low in bacterial/fungal/TB meningitis	>60% serum
Gram stain and culture (CPT 87205, 87070)	URGENT	ROUTINE	ROUTINE	Bacterial meningitis	No organisms
BioFire FilmArray ME Panel (CPT 87483)	URGENT	ROUTINE	-	Rapid pathogen identification (14 pathogens)	Negative
HSV-1/2 PCR (CPT 87529)	URGENT	ROUTINE	ROUTINE	HSV encephalitis (most common treatable cause)	Negative
Autoimmune encephalitis panel (CSF)	-	ROUTINE	ROUTINE	If clinical suspicion for autoimmune etiology	Negative
Cytology (CPT 88104)	-	ROUTINE	ROUTINE	Carcinomatous meningitis	Negative
VDRL (CSF)	-	ROUTINE	ROUTINE	Neurosyphilis	Negative
Oligoclonal bands (CPT 83916)	-	ROUTINE	ROUTINE	If demyelinating disease suspected	Negative or matched with serum

Special Handling: HSV PCR can be sent on refrigerated sample. Cytology requires rapid transport (<1 hour). Cell count must be processed within 1 hour.

Contraindications: Elevated ICP without imaging (CT first), coagulopathy (INR >1.5, platelets <50K), skin infection at LP site

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3. TREATMENT

3A. Acute/Emergent

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Lorazepam IV/IM (if actively seizing) (CPT 96374)	IM	-	0.1 mg/kg :: IV :: once :: 0.1 mg/kg IV (max 4 mg); may repeat once in 5 min	Respiratory depression, severe hypotension	RR, O2 sat, BP; have airway equipment ready	STAT	STAT	-	STAT
Midazolam IM (if no IV access)	IM	-	10 mg :: IM :: - :: 10 mg IM (if >40 kg) or 0.2 mg/kg IM	Respiratory depression	RR, O2 sat; have airway equipment ready	STAT	STAT	-	STAT
Midazolam intranasal (if no IV access)	IV	-	5 mg :: - :: - :: 5 mg per nostril (total 10 mg)	Respiratory depression	RR, O2 sat	STAT	STAT	-	STAT
Dextrose 50% IV	IV	-	25-50 mL :: IV :: - :: 25-50 mL IV if hypoglycemia confirmed or suspected	Hyperglycemia	Glucose	STAT	STAT	-	STAT
Thiamine IV	IV	-	100-500 mg :: IV :: - :: 100-500 mg IV BEFORE glucose if alcohol use suspected	None significant	None	STAT	STAT	-	STAT
Supplemental oxygen	INH	-	2-4 L :: INH :: PRN :: 2-4 L NC or non-rebreather as needed	None	O2 sat >94%	STAT	STAT	-	STAT
IV fluids (isotonic)	IV	-	N/A :: IV :: per protocol :: NS or LR bolus if hypotensive; maintenance if euvolemic	Fluid overload, severe hyponatremia	I/O, BP, Na	STAT	STAT	-	STAT
Flumazenil (rescue only)	IV	-	0.2 mg :: IV :: - :: 0.2 mg IV over 30 sec; may repeat 0.2 mg q1min to max 1 mg	Chronic benzodiazepine use; seizure history; tricyclic overdose	CAUTION: May lower seizure threshold and precipitate seizures; use only if severe respiratory depression unresponsive to supportive care	STAT	STAT	-	STAT

3B. Anti-Seizure Medications (ASMs) - Acute Loading

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Levetiracetam IV (CPT 96365)	IV	First-line acute loading	40-60 mg/kg :: IV :: - :: 40-60 mg/kg IV (max 4500 mg) over 15 min; OR 1500-3000 mg IV	None significant; reduce dose if CrCl <50	Somnolence, agitation (rare)	STAT	STAT	-	STAT
Levetiracetam PO	PO	Acute loading if stable	1500-3000 mg :: PO :: - :: 1500-3000 mg PO × 1, then start maintenance	Same	Same	URGENT	URGENT	URGENT	-
Fosphenytoin IV	IV	Alternative first-line	20 mg :: IV :: - :: 20 mg PE/kg IV at 150 mg PE/min (max rate)	AV block, sinus bradycardia, pregnancy (relative)	Continuous cardiac monitoring, BP; purple glove syndrome rare with fosphenytoin	STAT	STAT	-	STAT
Phenytoin IV	IV	If fosphenytoin unavailable	20 mg/kg :: IV :: - :: 20 mg/kg IV at max 50 mg/min	AV block, sinus bradycardia, pregnancy	Cardiac monitor, BP; give via large vein (tissue necrosis risk)	STAT	STAT	-	STAT
Valproate IV	IV	Alternative (broad-spectrum)	40 mg/kg :: IV :: - :: 40 mg/kg IV over 10 min (max 3000 mg)	Pregnancy (teratogenic - neural tube defects), hepatic disease, mitochondrial disease, urea cycle disorders	LFTs, ammonia, platelets; pancreatitis risk	STAT	STAT	-	STAT
Lacosamide IV	IV	Alternative first-line	200-400 mg :: IV :: - :: 200-400 mg IV over 15-30 min	PR prolongation >200 ms, 2nd/3rd degree AV block	ECG for PR interval; dizziness	URGENT	URGENT	-	URGENT

3C. Anti-Seizure Medications (ASMs) - Maintenance Therapy

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Levetiracetam	IV	First-line maintenance	500-1500 mg :: IV :: BID :: 500-1500 mg PO/IV BID; start 500 mg BID, may increase by 500 mg/dose weekly; max 3000 mg/day	Renal impairment (adjust per CrCl)	Behavioral changes (irritability, depression - "Keppra rage"); renal function	-	ROUTINE	ROUTINE	ROUTINE
Lamotrigine	-	First-line (especially women of childbearing potential)	25 mg :: PO :: daily :: Start 25 mg daily × 2 weeks; then 50 mg daily × 2 weeks; then 100 mg daily; target 200-400 mg/day in divided doses	Slow titration required (SJS/TEN risk)	Rash (stop if any rash; SJS/TEN risk higher with fast titration or valproate co-therapy)	-	ROUTINE	ROUTINE	-
Lacosamide	PO	First-line alternative	100 mg :: PO :: BID :: Start 100 mg PO BID; increase by 100 mg/day weekly; target 200-400 mg BID; max 400 mg BID	PR prolongation, 2nd/3rd degree AV block, severe hepatic impairment	ECG at baseline and dose changes; dizziness, diplopia	-	ROUTINE	ROUTINE	ROUTINE
Oxcarbazepine	PO	Focal seizures	300 mg :: PO :: BID :: Start 300 mg PO BID; increase by 300-600 mg/day every week; target 1200-2400 mg/day in divided doses	Hypersensitivity to carbamazepine	Sodium (hyponatremia in 2-3%); HLA-B*1502 screening in at-risk populations	-	ROUTINE	ROUTINE	-
Carbamazepine	PO	Focal seizures	200 mg :: PO :: BID :: Start 200 mg PO BID; increase by 200 mg/day weekly; target 800-1200 mg/day; max 1600 mg/day	AV block; bone marrow suppression; concurrent MAOIs	CBC, LFTs, sodium at baseline and periodically; HLA-B*1502 screening	-	ROUTINE	ROUTINE	-
Valproate/Divalproex	PO	Generalized seizures	10-15 mg/kg :: PO :: - :: Start 10-15 mg/kg/day in divided doses; increase by 5-10 mg/kg/week; target 1000-2000 mg/day; max 60 mg/kg/day	Pregnancy (teratogenic); hepatic disease; mitochondrial disease; pancreatitis history	LFTs, ammonia, CBC, platelets at baseline, then q3-6mo; weight gain, hair loss, tremor	-	ROUTINE	ROUTINE	ROUTINE
Phenytoin	PO	Focal or generalized	300-400 mg :: PO :: daily :: 300-400 mg daily (extended release) or divided TID (immediate release); adjust by level	Pregnancy (relative - fetal hydantoin syndrome); AV block	Free phenytoin level (target 1-2 μg/mL); total level 10-20 μg/mL; CBC, LFTs; gingival hyperplasia, hirsutism	-	ROUTINE	ROUTINE	ROUTINE
Brivaracetam	PO	Alternative to levetiracetam	50 mg :: PO :: BID :: Start 50 mg PO BID; may increase to 100 mg BID; max 200 mg/day	Hepatic impairment (reduce dose)	Less behavioral side effects than levetiracetam; somnolence	-	ROUTINE	ROUTINE	ROUTINE
Zonisamide	PO	Adjunctive or monotherapy	100 mg :: PO :: daily :: Start 100 mg daily; increase by 100 mg every 2 weeks; target 300-400 mg daily; max 600 mg/day	Sulfonamide allergy; kidney stones	Kidney stones (carbonic anhydrase inhibitor); oligohidrosis (pediatric); metabolic acidosis	-	-	ROUTINE	-
Topiramate	PO	Adjunctive or monotherapy	25 mg :: PO :: BID :: Start 25 mg BID; increase by 50 mg/day weekly; target 200-400 mg/day in divided doses; max 400 mg/day	Kidney stones; metabolic acidosis; glaucoma	Cognitive impairment ("dopamax"); paresthesias; kidney stones; weight loss	-	-	ROUTINE	-
Clobazam	PO	Adjunctive therapy	5-10 mg :: PO :: daily :: Start 5-10 mg daily; increase by 5-10 mg weekly; max 40 mg/day in divided doses	Severe hepatic impairment; sleep apnea (untreated)	Sedation; tolerance may develop; CYP2C19 poor metabolizers need lower dose	-	ROUTINE	ROUTINE	-
Perampanel	PO	Adjunctive for focal or GTCS	2 mg :: PO :: qHS :: Start 2 mg qHS; increase by 2 mg weekly; target 8-12 mg qHS; max 12 mg/day	None absolute	Psychiatric effects (aggression, hostility); dizziness; take at bedtime; Schedule III	-	-	ROUTINE	-
Cenobamate	PO	Adjunctive for focal	12.5 mg :: PO :: daily :: Start 12.5 mg daily × 2 weeks; titrate slowly per package insert; target 200-400 mg daily	Familial short QT syndrome	Very slow titration required (DRESS risk); QT shortening; titration pack available	-	-	ROUTINE	-
Phenobarbital	IV	Refractory or resource-limited	15-20 mg/kg :: IV :: - :: Load 15-20 mg/kg IV; maintenance 1-3 mg/kg/day (60-180 mg/day); target level 15-40 μg/mL	Porphyria; severe respiratory disease	Sedation; cognitive effects; drug interactions (CYP inducer); level monitoring	-	ROUTINE	ROUTINE	ROUTINE

3D. Symptomatic Treatments

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Acetaminophen	IV	Post-ictal headache	650-1000 mg :: IV :: q6h :: 650-1000 mg PO/IV q6h PRN; max 3000 mg/day (2000 mg if liver disease)	-	Severe hepatic impairment	LFTs if chronic use	URGENT	ROUTINE	ROUTINE	URGENT
Ibuprofen	PO	Post-ictal headache	400-600 mg :: PO :: PRN :: 400-600 mg PO q6-8h PRN; max 2400 mg/day	-	Renal impairment; GI bleed; post-CABG	Renal function if prolonged use	-	ROUTINE	ROUTINE	-
Ondansetron	IV	Post-ictal nausea	4-8 mg :: IV :: q8h :: 4-8 mg IV/PO q8h PRN	-	QT prolongation; severe hepatic impairment	QTc if multiple doses	URGENT	ROUTINE	ROUTINE	URGENT
Lorazepam	IV	Post-ictal agitation (if severe)	0.5-2 mg :: IV :: PRN :: 0.5-2 mg IV/PO PRN; use with caution	-	Respiratory depression; altered mental status	RR, sedation level; avoid if post-ictal confusion resolving	URGENT	URGENT	-	URGENT
Sertraline	PO	Depression/anxiety (chronic)	50 mg :: PO :: daily :: Start 50 mg daily; increase by 25-50 mg q1-2 weeks; max 200 mg daily	-	Concurrent MAOIs	Suicidality monitoring weeks 1-4	-	-	ROUTINE	-
Escitalopram	PO	Depression/anxiety (chronic)	10 mg :: PO :: daily :: Start 10 mg daily; max 20 mg daily	-	Concurrent MAOIs; QT prolongation	QTc if risk factors	-	-	ROUTINE	-
Melatonin	PO	Sleep disturbance	3-5 mg :: PO :: qHS :: 3-5 mg PO qHS	-	None significant	Well tolerated; may help with ASM-related sleep disruption	-	ROUTINE	ROUTINE	-
Trazodone	PO	Insomnia	25-100 mg :: PO :: qHS :: 25-100 mg PO qHS	-	Concurrent MAOIs	Orthostatic hypotension; priapism (rare)	-	ROUTINE	ROUTINE	-

3E. Second-line/Refractory

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Add second ASM	-	-	N/A :: - :: per protocol :: Choose complementary mechanism; see maintenance options	Per specific agent	Per specific agent	-	ROUTINE	ROUTINE	ROUTINE
Epilepsy surgery evaluation referral	-	-	N/A :: - :: once :: For drug-resistant epilepsy (failed 2+ appropriately chosen ASMs)	N/A	N/A	-	EXT	EXT	-
Vagus nerve stimulator (VNS)	-	-	N/A :: - :: continuous :: For drug-resistant epilepsy not surgical candidates	N/A	Device checks	-	-	EXT	-
Dietary therapy (ketogenic diet, modified Atkins)	-	-	N/A :: - :: daily :: For drug-resistant epilepsy	Fatty acid oxidation disorders; pyruvate carboxylase deficiency	Metabolic panels; lipids; kidney function	-	-	EXT	-

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4. OTHER RECOMMENDATIONS

4A. Referrals & Consults

Recommendation	ED	HOSP	OPD	ICU	Indication
Neurology consult	URGENT	URGENT	ROUTINE	URGENT	All new onset seizures for evaluation and management
Epilepsy specialist referral	-	ROUTINE	ROUTINE	-	Diagnostic uncertainty, refractory seizures, surgical candidacy
EEG technologist/neurodiagnostics	URGENT	URGENT	ROUTINE	URGENT	EEG scheduling; continuous EEG if indicated
Neurosurgery consult	-	URGENT	EXT	URGENT	Structural lesion requiring intervention (tumor, AVM, SDH)
Medical toxicology consult	URGENT	ROUTINE	-	URGENT	Suspected drug/toxin-induced seizure
Infectious disease consult	-	URGENT	-	URGENT	CNS infection confirmed or suspected
Oncology consult	-	ROUTINE	ROUTINE	-	Brain tumor identified
Psychiatry consult	-	ROUTINE	ROUTINE	-	Depression, anxiety post-diagnosis; psychogenic non-epileptic spells suspected
Social work consult	-	ROUTINE	ROUTINE	-	Driving restrictions impact, employment concerns, insurance navigation
Occupational therapy	-	ROUTINE	ROUTINE	-	Work safety evaluation, activity modification
Physical therapy	-	ROUTINE	ROUTINE	-	If post-ictal weakness, falls, injury from seizure
Neuropsychology referral	-	-	ROUTINE	-	Cognitive complaints, pre-surgical evaluation
Women's health/OB-GYN	-	-	ROUTINE	-	Contraception counseling (ASM interactions), pregnancy planning
Epilepsy monitoring unit (EMU) admission	-	EXT	EXT	-	Characterize seizure type, video-EEG monitoring, pre-surgical evaluation
Driving evaluation/rehabilitation	-	-	EXT	-	Return to driving assessment when eligible

4B. Patient Instructions

Recommendation	ED	HOSP	OPD
Return to ED immediately if: recurrent seizure, prolonged seizure >5 minutes, head injury, persistent confusion, difficulty breathing, or status epilepticus	✓	✓	✓
Do NOT drive until cleared by neurology (driving restrictions per state guidelines; typically require seizure-free interval)	✓	✓	✓
Avoid operating heavy machinery, working at heights, or swimming alone	✓	✓	✓
Do not bathe alone; showers preferred over baths; keep bathroom door unlocked	✓	✓	✓
Inform employer if job involves safety-sensitive duties	-	✓	✓
Take ASM exactly as prescribed; do NOT stop abruptly (risk of breakthrough seizures or status epilepticus)	✓	✓	✓
Avoid common seizure triggers: sleep deprivation, alcohol, illicit drugs, missed medications	✓	✓	✓
Keep a seizure diary: date, time, duration, description, triggers, post-ictal symptoms	-	✓	✓
Wear medical identification (bracelet or necklace)	-	✓	✓
Educate family/coworkers on seizure first aid: stay with person, protect head, do NOT put anything in mouth, time the seizure, call 911 if >5 minutes	✓	✓	✓
Follow up with neurology within 1-2 weeks of discharge	✓	✓	-
Bring list of all medications (including OTC and supplements) to all appointments - many interact with ASMs	-	✓	✓
Women: discuss contraception with provider; some ASMs reduce efficacy of hormonal contraception	-	✓	✓
Report side effects (mood changes, rash, dizziness, cognitive issues) promptly; do NOT stop medication without calling	-	✓	✓
Avoid flashing/strobe lights if photosensitive seizures suspected	-	✓	✓

4C. Lifestyle & Prevention

Recommendation	ED	HOSP	OPD
Sleep hygiene: aim for 7-9 hours nightly; maintain regular sleep schedule	-	✓	✓
Avoid alcohol (lowers seizure threshold; interacts with ASMs)	✓	✓	✓
Avoid illicit drugs (especially stimulants: cocaine, amphetamines)	✓	✓	✓
Stress management techniques	-	-	✓
Regular moderate exercise (not extreme sleep deprivation from overtraining)	-	-	✓
Medication adherence: use pill organizers, phone alarms, refill reminders	-	✓	✓
Folic acid supplementation 1-4 mg daily for women of childbearing potential (especially if on enzyme-inducing ASMs)	-	✓	✓
Bone health: vitamin D 1000-2000 IU daily; calcium as needed (enzyme-inducing ASMs affect bone density)	-	-	✓
Avoid known personal triggers (flashing lights, certain foods, stress, if identified)	-	✓	✓
Home safety modifications: pad sharp furniture corners, avoid glass shower doors, use microwave instead of stovetop when alone	-	✓	✓
Seizure alert devices or apps for those living alone (optional)	-	-	✓
Smoking cessation (increases ASM metabolism; general health)	-	✓	✓

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═══════════════════════════════════════════════════════════════ SECTION B: REFERENCE (Expand as Needed) ═══════════════════════════════════════════════════════════════

5. DIFFERENTIAL DIAGNOSIS

Alternative Diagnosis	Key Distinguishing Features	Tests to Differentiate
Syncope (convulsive syncope)	Brief (<15 sec), triggered by standing/Valsalva/micturition, rapid recovery, no post-ictal confusion, possible prodrome (lightheaded, tunnel vision)	ECG, orthostatic vitals, tilt table test, echocardiogram
Psychogenic non-epileptic spells (PNES)	Variable/atypical semiology, prolonged duration, preserved awareness with bilateral movements, eye closure, pelvic thrusting, no post-ictal confusion, psychiatric comorbidity	Video-EEG capturing event; normal prolactin
Transient ischemic attack (TIA)	Negative symptoms (weakness, numbness), no LOC, no convulsive activity	MRI DWI, vascular imaging
Migraine with aura	Gradual onset, spreading symptoms, headache follows, stereotyped	Clinical history, normal EEG
Hypoglycemia	Diaphoresis, tremor, confusion, rapid glucose corrects symptoms	Fingerstick glucose
Cardiac arrhythmia	Palpitations, sudden LOC without warning, rapid recovery	ECG, Holter monitor, event recorder, EP study
Transient global amnesia	Isolated anterograde amnesia, repetitive questioning, no convulsive activity	Clinical presentation (self-limited), MRI DWI (hippocampal)
Sleep disorders (parasomnias, cataplexy)	Occur from sleep, specific features (cataplexy with emotion)	Sleep study, clinical history
Movement disorders (dystonia, tics)	Stereotyped, no LOC, suppressible (tics), may have sensory urge	Clinical history, video
Drug intoxication/withdrawal	History of substance use, known withdrawal timeline	Toxicology screen, history
Metabolic encephalopathy	Gradual onset, diffuse abnormality, asterixis, no discrete seizures	Labs (ammonia, glucose, Na), EEG (diffuse slowing)

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6. MONITORING PARAMETERS

Parameter	Frequency	Target/Threshold	Action if Abnormal
Neurologic exam (level of consciousness, focal deficits)	Q1-2h in ED; Q4h inpatient; each visit OPD	Return to baseline	If prolonged post-ictal state: continuous EEG to rule out non-convulsive status
Vital signs	Continuous in ED/ICU; Q4h floor	Stable	Treat hyperthermia, hypotension, hypoxia
Glucose	On arrival; repeat if altered	>70 mg/dL	Dextrose if low
Electrolytes (Na, Ca, Mg)	On arrival; daily if abnormal	Normal ranges	Correct deficiencies; identify cause
ASM level (phenytoin, valproate, phenobarbital, carbamazepine)	Trough level 5-7 days after initiation or dose change; PRN	Therapeutic range (drug-specific)	Adjust dose; check free level for phenytoin

ASM Therapeutic Level Reference: | ASM | Therapeutic Range | Notes | |-----|-------------------|-------| | Phenytoin (total) | 10-20 μg/mL | Check FREE level (1-2 μg/mL) if hypoalbuminemia, renal failure, or pregnancy | | Valproate | 50-100 μg/mL | Higher levels may be needed; monitor for toxicity | | Carbamazepine | 4-12 μg/mL | Autoinduction occurs over 2-4 weeks | | Phenobarbital | 15-40 μg/mL | Sedation common at higher levels | | Lacosamide | 10-20 μg/mL | Level monitoring not routinely required | | Levetiracetam | 12-46 μg/mL | Level monitoring not routinely required; clinical response guides dosing | | LFTs | Baseline; q3-6 months on valproate, carbamazepine | Normal | Discontinue if hepatotoxicity; hold if transaminases >3× ULN | | CBC | Baseline; q3-6 months on carbamazepine, valproate | Normal | Discontinue if significant bone marrow suppression | | Sodium | Baseline; periodically on oxcarbazepine, carbamazepine | >130 mEq/L | Reduce dose or switch if severe hyponatremia | | EEG | Within 24-48h of first seizure; repeat if diagnosis unclear | No ongoing seizures | Adjust treatment if epileptiform activity or non-convulsive seizures | | MRI brain | Within 2 weeks of first seizure; sooner if structural cause suspected | No new lesions | Address structural cause; refer to appropriate specialist |

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7. DISPOSITION CRITERIA

Disposition	Criteria
Discharge home	Single, self-limited seizure; returned to baseline; no dangerous etiology identified on initial workup; reliable adult supervision for 24h; ASM initiated or deferred with close follow-up; outpatient EEG and MRI arranged; understands return precautions and driving restriction
Admit to floor (observation)	Prolonged post-ictal period; multiple seizures; new structural lesion requiring monitoring; ASM loading requiring observation; social situation preventing safe discharge; need for inpatient EEG; new focal neurologic deficit
Admit to ICU	Status epilepticus (current or recent); recurrent seizures despite treatment; need for continuous EEG monitoring; airway compromise; hemodynamic instability; significant aspiration; large structural lesion with mass effect; CNS infection
Transfer to higher level	MRI unavailable; EEG unavailable; neurology not available for consultation; need for neurosurgical intervention unavailable at facility

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8. EVIDENCE & REFERENCES

Recommendation	Evidence Level	Source
ILAE 2017 seizure classification	Class I	Fisher RS et al. Epilepsia 2017
ILAE 2014 practical definition of epilepsy	Class I	Fisher RS et al. Epilepsia 2014
EEG within 24-48h increases yield	Class II, Level B	AAN Practice Parameter 2007
MRI superior to CT for epilepsy evaluation	Class I, Level A	ILAE Neuroimaging Task Force 2019
Levetiracetam non-inferior to phenytoin for acute seizure cessation	Class I, Level A	ESETT Trial, Kapur et al. NEJM 2019
Risk of recurrence after first unprovoked seizure ~40-50%	Class I	Hauser et al. NEJM 1998
Starting ASM after first seizure reduces recurrence but not long-term remission	Class I, Level A	FIRST Trial; MESS Trial, Marson et al. Lancet 2005
Lamotrigine and levetiracetam preferred in women of childbearing potential	Class II, Level B	AAN/AES Guidelines 2009; MONEAD Study
Driving restrictions reduce accident risk	Class II, Level B	Multiple observational studies
Prolactin elevation supports diagnosis of epileptic seizure (if drawn <20 min)	Class II, Level B	Chen et al. Neurology 2005
Continuous EEG detects non-convulsive status in altered patients	Class II, Level B	Claassen et al. Neurology 2004
Folate supplementation reduces teratogenicity risk	Class II, Level B	AAN/AES Practice Parameter 2009

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CHANGE LOG

v1.1 (January 13, 2026) - Updated levetiracetam loading dose to range (40-60 mg/kg) per physician preference - Added phosphorus to core labs (hypophosphatemia in alcohol withdrawal) - Added flumazenil to acute treatments with seizure threshold caution - Added note that CT insufficient for etiology; MRI is gold standard - Updated driving restriction language to generic "per state guidelines" - Added ASM therapeutic level reference table to Section 6 - Added ILAE 2017 seizure classification and 2014 epilepsy definition to references

v1.0 (January 13, 2026) - Initial creation - Comprehensive ASM section with individual drug rows and complete dosing - Included 14 maintenance ASMs with titration schedules - Added acute loading options (levetiracetam, fosphenytoin, valproate, lacosamide) - LP section for infectious/autoimmune workup - Extensive differential diagnosis including syncope, PNES, cardiac causes - Complete patient instructions including driving, safety, seizure first aid - Setting-appropriate coverage across ED, HOSP, OPD, ICU