julia b. toub, md/media/files/providence or... · 2018. 12. 4. · leah • 44 y.o. female hx/o...

Julia B. Toub, MD

Providence Neuroscience Symposium

November 29, 2018

I have no financial relationships to

disclose.

1. Seizure: the clinical manifestation of an abnormal and

excessive synchronization of a population of cortical

neurons.

2. Practical definition of epilepsy (2014)

– ≥ 2 unprovoked seizures separated by at least 24 hours.

– 1 unprovoked (or reflex) seizure and a probability of further

seizures similar to the general recurrence risk (at least 60%)

after two unprovoked seizures, occurring over the next 10

years.

• EEG

• MRI

• Epilepsy Syndrome

• Worldwide prevalence ~ 50,000,000, underestimated due to:

– Limited access to healthcare

– Social/cultural stigma

• ~3,000,000 Americans

• As common as breast cancer with a similar mortality

• 8-10% of the population will have a seizure at some point in

their lives; 1-3% will be diagnosed with epilepsy.

• 4th most common neurological disease after migraine,

stroke, and Alzheimer’s disease

https://www.cdc.gov/epilepsy/data/index.html

Leah

• 44 y.o. female hx/o migraine w/aura and depression.

• New onset GTC out of sleep lasting 1 minute.– + incontinence

– - tongue bite

– No personal history of seizure.

– FH: Brother with childhood seizures.

– SH: • EtOH 1 glass of wine with dinner.

• Drives school bus.

– Remote concussion with indeterminate loss of consciousness.

• VS: T 37, BP 120/80, P 90

• Meds: Nortriptyline, sumatriptan

• CT head: No acute abnormality.

• EEG: Sharply-contoured intermittent right frontal slowing.

Arnold

• 52 y.o. male hx/o HTN, DM, chronic back pain.

• New onset GTC while at work lasting 2.5 minutes.– + incontinence

– + tongue bite

– No personal or family hx of seizure.

– Remote concussion w/o LOC.

– FH: Dad with alcohol-withdrawal seizures.

– SH: EtOH 1-2 beers per night, no other drugs.

– Works in IT, desk job

• VS: T 37.5, BP 215/115, P 130

• Meds: Metoprolol, linsinopril, ASA, tizanidine, tramadol, metformin.

• CT head: Chronic microvascular change.

• EEG: Rare intermittent generalized slowing.

• Isolated unprovoked generalized tonic-clonic seizure:

– History

– CMP

– CBC

– Tox screen

– Driving restriction

– EEG (ideally within 24 hours of seizure)

– Pregnancy test

– CT/MRI: MRI ideal

• Provoked seizure: Remove offending agent

• Beware of “seizure mimics”

– Transient Ischemic Attack

– Metabolic Disturbance

– Sleep Disorders

– Syncope and Convulsive Syncope

– Non-epileptic spells

• Misdiagnosis is usually worse than delayed diagnosis

In many circumstances, we no longer wait for a second unprovoked seizure to evaluate and treat.

In almost all cases, a patient with a single unprovoked seizure and one of the following should be started on antiepileptic medications:

• EEG WITH EPILEPTIFORM ACTIVITY

– Electroencephalogram within 24-48 hours has a 70% yield

– Sleep deprived EEG has additional 13-31% yield

• ABNORMAL BRAIN MRI (3T PREFERRED)

– Prior stroke

– Prior evidence of trauma/encephalomalacia

– Malformation of cortical development

– Tumor

• NOCTURNAL SEIZURE

Provoked, no brain injury: 3%

Provoked, brain injury: 10%

Single, Unprovoked: 42%

Pohlmann-Eden, BMJ, 2006

Recurrent, Unprovoked: 70-80%

• Psychiatric: Buproprion (common), Clozapine

• Analgesic: Tramadol (common), Tapentadol

• Antibiotics: PCN, Cephalosporins, Imipenem, Amphotericin

B

• Pulmonary: Aminophylline

• Immunologic: Cyclosporin

• Pre/peri-natal injury

• Febrile convulsions

• Developmental History

• Head trauma with loss of consciousness

• Family history of seizures (unprovoked)

• Brain tumor, stroke, or other cortical/structural brain lesion

• History of meningitis/encephalitis

Arnold



– + tongue bite






• VS: T 37.5, BP 215/115, P 130




Probable provoked seizure

• Tramadol

• Hypertensive urgency

• No definte risk factors for

seizure recurrence.

Recs:

• Cerebrovascular risk factor

control.

• Stop tramadol

• Driving restriction

• Monitor off AEDs

Chronic microvascular

ischemic changes on T2/FLAIR

Arnold



– + tongue bite






• VS: T 37.5, BP 215/115, P 130




Probable provoked seizure

• Tramadol

• Hypertensive urgency

• MRI with PRES/RPLS

Recs:

• Cerebrovascular risk factor control.


• Stop tramadol

• Treatment with AEDs in the short

term (acute pathology).

T2-weighted hyperintense

(white) signal involving

bilateral parietal and occipital

lobes (PRES/RPLS)

Leah

• 44 y.o. female hx/o migraine w/aura and depression.

• New onset GTC out of sleep lasting 1 minute.– + incontinence

– - tongue bite

– No personal history of seizure.

– FH: Brother with childhood seizures.

– SH: • EtOH 1 glass of wine with dinner.

• Drives school bus.

– Remote concussion with indeterminate loss of consciousness.

• VS: T 37, BP 120/80, P 90

• Meds: Nortriptyline, sumatriptan, tramadol (PRN)

• CT head: No acute abnormality.

• EEG: Sharply-contoured intermittent right frontal slowing.

High probability for seizure recurrence

• Nocturnal seizure

• + Family history

• EEG suggestive of focality but nothing

clearly epileptiform.

• + structural abnormality

• +/- head trauma w/LOC

Employment risk

Recs:


• Treat with AED: TPM

(postmenopausal) or LTG

Previously Simple Partial

Previously Complex Partial, focal dyscognitive

• Frontal:– Primary motor area: “Jacksonian march”

– Supplementary motor area (SMA): “Hypermotor”, asymmetric tonic, brief, may lack postictal period.

• Lateral Temporal:– Auditory/visual hallucinations, language impairment (dominant)

• Mesial Temporal: – Epigastric/olfactory/gustatory aura, déjà vu, jamais vu, fear, orolingual

automatisms, dysautonomia, “impending doom.”

– Interictal memory complaints, dysphoria

• Parietal:– Somatosensory symptoms, visual illusions/hallucinations, distortions

of body image.

• Occipital:– Visual hallucinations

• Diagnosis:– Establishing a diagnosis (epileptic vs. nonepileptic events)

– Characterization of epilepsy (generalized vs. focal)

– Identification of epilepsy syndrome

– Identify triggers (photosensitivity, sleep deprivation)

• Management:– Assessing risk of recurrence after single unprovoked seizure

– Guiding selection of appropriate anticonvulsant

– Localizing seizure focus

– Surgical planning

– Assessing mental status change

– Evaluating for nonconvulsive status epilepticus

– Monitoring/guiding treatment in status epilepticus

– Risk stratification for seizure recurrence prior to taper off anticonvulsants

– Prognostication in the ICU setting

Advantages Limitations

Measure of brain function complements

neuroimaging

Relatively low sensitivity for IEDs

Relatively non-invasive Influenced by state of alertness,

medications, and other metabolic

factors

May be the only test abnormal in

epileptic patients

Subjectivity

Low cost Potential for false localization

Low morbidity Small/deep discharges may produce no

changes on scalp EEG

Ambulatory/portable options Artifact

• Confirm a diagnosis of epilepsy (+/-)

• Determine seizure subtype (history, EEG, imaging)

• How quickly does medication needs to be introduced?

• Consider comorbid conditions, social circumstances,

finances, etc.

• Cost

• Mechanism of action

BROAD SPECTRUM NARROW SPECTRUM

OLDER • Valproic Acid/Divalproex * VPA)

• Clonazepam (CZP)

• Carbamazepine (CBZ) (focal)

• Ethosuximide (ESX/ETX/ESM) (absence)

• Phenobarbital (PB) (focal>generalized)

• Phenytoin (PHT) (focal>generalized, status epilepticus)

• Primidone (PRM) (focal)

NEWER • Lamotrigine * (LTG)

• Levetiracetam * (LEV)

• Topiramate * (TPM)

• Zonisamide (ZNS)

• Perampanel (PER)

• Brivaracetam (BRV) (focal)

• Cannabidiol (CBD) (Lennox Gastaut, Dravet)

• Clobazam (CLB) (Lennox Gastaut)

• Eslicarbazepine (ESL) (focal)

• Felbamate (FBM) (focal; severe refractory)

• Gabapentin (GBP) (focal)

• Lacosamide (LCM) (focal)

• Oxcarbazepine* (OXC) (focal)

• Pregabalin (PRG) (focal)

• Rufinamide (RFM) (Lennox Gastaut)

• Tiagabine (TGB) (focal)

• Vigabatrin (VGB) (focal, infantile spasms)

* Available in once-daily extended release formulation

• Newer AEDs have fewer side-effects.

• Choose broad spectrum coverage if unsure of seizure

subtype:

1. Levetiracetam

2. Lamotrigine

3. Valproic acid

4. Topiramate

5. Zonisamide (approved only as an adjunct in treatment of

partial seizures, though it does have broad-spectrum

efficacy).

• Focal epilepsy agents can exacerbate generalized

epilepsies

– CBZ, OXC, ESL, GBP, PRG

Conditions/Circumstances AED Selection

Unsure what epilepsy type

Mood disorder

Migraines

Chronic Pain

Pregnancy

Hepatic dysfunction

Problems with medication adherence

LEV, LTG, VPA, ZNS, TPM

LTG, VPA, OXC (if focal)

TPM, ZNS, PRG, GBP, CBZ

GBP, PRG, CBZ

LEV, LTG, possibly ZNS

LEV

AED with XR formulation (LTG, LEV,

TPM, OXC) or long half life (ESL, ZNS)

Drug(s) Cautions

LEV, BRV, PER

LTG, (CBZ, OXC, ESL-Asian)

PHT, CBZ, OXC, PHB, PRM, and VPA

VPA, FBM

PHT, PHB, CBZ, PHB, PRM, VPA, FBM, CBD

LEV, GBP, PRG

TPM, ZNS

CBZ, OXC, ESL

VPA, FBM, LTG, CBZ, PHB

VPA

LTG, LEV

Depression, irritability, psychosis, anxiety, homicidal ideation

(PER).

Stevens-Johnson syndrome (rapid initiation, concurrent use of VPA)

and other skin reactions.

Vitamin D deficiency, osteoporosis

Weight gain

Many drug-drug interactions (especially warfarin), hepatotoxic

May require dose adjustment if renal impairment.

Cognitive slowing, weight loss, renal calculi. Acute angle closure

glaucoma (TPM), sulfa allergy (ZNS)

Hyponatremia

Blood dyscrasias

Hyperammonemia

Adjustment in dose during pregnancy; LTG dose change with OCPs

• Women of childbearing age

– LTG and LEV safest

– Potential for teratogenicity of ALL AEDs

– Newer AEDs better than older AEDs

– Folic acid in ALL women of childbearing potential

– LTG and LEV levels drop in pregnancy

– Other AEDs: Possible reduction in contraceptive efficacy;

secondary contraception should be used.

• Women of all ages

– LTG: Estrogen-containing OCPs increases LTG clearance

and may decrease levels.

– VPA: Hirsutism, weight gain, alopecia

• Not appropriate for most

patients with seizure

• CBD antiepileptic properties

• THC may make seizures worse

• Recreational and medical

dispensaries poorly regulated

• New FDA formulation Epidiolex

for patients with Lennox-Gastaut

and Dravet Synromes.

• ~1/3 epileptic patients

• Several surgical and non-surgical options for patients living

with medically refractory seizures.

– Epilepsy surgery (focal epilepsy): Resection, laser ablation

– RNS (focal epilepsy)

– VNS (focal and generalized epilepsy)

– Diet (focal and generalized epilepsy)

• Medically refractory cases should be managed at an

epilepsy center.

• Elective admission for diagnostic purposes, seizure

classification, medication titration, and/or pre-surgical

evaluation

• Continuous video EEG monitoring

• Candidates:

– Patients with or without diagnosis of epilepsy experiencing

continued seizures despite therapeutic levels of AEDs

– Patients requiring expedient medication adjustment in a

controlled atmosphere

– Patients undergoing pre-surgical evaluation

– Patients with deficits out of proportion to reported seizure

frequency (e.g. persistent memory problems, weakness)

• Introduce stressors to provoke events in question:

– Reduced/discontinuation of medications

– Sleep deprivation

– Hyperventilation

– Photic stimulation

– Exposure to agents known to provokes seizures in individual

patients

• Important to capture ALL of the patient’s events

*Some patients may have epileptic and nonepileptic events.

• Epilepsy is common.

• Treatment may be warranted after a single unprovoked seizure on

the basis of EEG, MRI, and history.

• All that shakes is not seizure; All seizures do not shake.

• There is no one-size fits all approach to epilepsy management.

• When seizure subtype isn’t clear, choose a broad-spectrum AED.

• Use of the EMU to differentiate between epileptic and non-

epileptic events is imperative to providing patients with

appropriate treatment when there is diagnostic uncertainty.

• Non-epileptic events do not preclude the coexistence of epileptic

seizures.

julia b. toub, md/media/files/providence or... · 2018. 12. 4. · leah • 44 y.o. female hx/o...

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