Fits, Faints and Fosphenytoin: Pediatric Seizures
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1 Fits, Faints and Fosphenytoin: Pediatric Seizures Kevin C. Ess, MD, PhD Chief, Division of Pediatric Neurology Departments of Pediatrics Vanderbilt University Medical Center
2 Disclosure Kevin Ess was the P.I. for an open label study of lacosamide (Vimpat) for prevention of complex partial seizures in children, sponsor UCB Pharma (ended August 2016) Research Funding: -NINDS, NIH -Alternating Hemiplegia of Childhood Foundation
3 Objectives lreview common seizure types and epilepsy syndromes seen in children lreview current medical therapies for epilepsy in children lreview additional epilepsy therapies including diet, surgery, and alternative medications
4 Overview Seizure and Epilepsy definitions Specific Pediatric Syndromes Differential Diagnosis of Seizures Treatment options Old Medications Newer medications Cannabinoids (CBD) Ketogenic diet Surgery Vagal Nerve Stimulator (VNS) Resection
5 Brain Complexity Billions of neurons in our brains that make trillions of connections with each other Problems happen
6 Seizure An electrical discharge of neurons in the brain that causes an observable change in behavior
7 Epilepsy 2 or more unprovoked seizures Classification: -Generalized -Partial -Simple -Complex
8 EEG (electroencephalogram) Records electrical activity of the brain Can be used to determine if normal patterns are present Example, age related patterns Can be used for epilepsy-related patterns Example: spikes, sharp waves Useful for diagnosis of type of epilepsy and specific syndromes
9 Generalized Seizures
10 Childhood Absence Epilepsy Clinical presentation of staring spells petit mal Age 4-10 Characteristic EEG changes Most patients outgrow syndrome by age 11-15
11 Generalized Tonic Clonic (GTC) The Big One Stiffness (tonic phase) followed by rhythmic shaking (clonic phase) Longer than 5 minutes a medical emergency (status epilepticus) -treatment lorazepam (Ativan), valium (Diastat), fosphenytoin Can be as a GTC or start focally and spread to become GTC
12 Infantile Spasms Typically start around age 6 months Startle -like movements One common cause is tuberous sclerosis EEG- hypsarrhymia Treatments ACTH vigabatrin topiramate (Topamax)
13 Hypsarrythmia
14 Lennox-Gastaut Syndrome Multiple Seizure types Atypical Absence Seizures Tonic Seizures (during sleep) Atonic Seizures Abnormal development, mental retardation Specific EEG Changes Generally occurs before age 10
15 Juvenile Myoclonic Epilepsy (JME) Generalized Epilepsy Absence Seizures GTC Seizures Myoclonic jerks (AM often) Tends not to remit Usually easily treated with valproic acid (Depakote) or levitracetam (Keppra)
16 Juvenile Myoclonic Epilepsy
17
18 Focal (Partial) Seizures -Simple -Dyscognitive (Complex) -altered mental status
19 Benign Rolandic Epilepsy (BRE) lbenign epilepsy with centro-temporal spikes (BECTS) ldiagnosis based on clinical presentation and EEG lrelatively common loften nocturnal seizures lstarts age 2-12 years, most 5-10 years lmost patients grow out of it by age 16
20 -Medscape
21 Excess Mortality Rate of Epilepsy Patients who have Seizures 1% Olafsson et al. Epilepsia 1998
22 Sudden Unexpected Death in Epilepsy (SUDEP) lthe patient has epilepsy ldied unexpectedly while in reasonable health lfatal attack occurred suddenly ldeath occurred during normal activities lobvious medical cause cannot be found lexcluded in status epilepticus or acute trauma
23 Mimickers of Epilepsy lbreath-holding spells lsyncope lhemiplegia lmigraine lmovement Disorders lfebrile Seizures l Pseudoseizures non-epileptic seizures/spells
24 Syncopal Events nshared Pathophysiology of Syncope, Breath Holding Spells, others -Events that occur at the hairdresser, church, dentist, blood draw, etc. nvagal-mediated bradycardia with brain hypoperfusion -altered mental status -potential anoxic seizure
25 Overall Treatment Strategies-Medical -Why treat? -seizure control -quality of life, education, development -minimize SUDEP -Many drugs now -Better side effect profile -Medications should be selected based on syndrome, patient specific issues, tolerability, side effects
26 Treatments-Medical - Levetiracetam (Keppra) -focal and generalized seizures -well tolerated generally -may cause irritability behavioral issues (role for vitamin B6) -mechanism: binds presynaptic protein SV2A, may inhibit Ca channels -Oxcarbazepine (Trileptal) -partial seizures -hyponatremia -can make generalized seizures worse -mechanism: sodium channel inhibitor -Carbamazepine (Tegretol, Carbatrol) -partial seizures -can make generalized seizures worse
27 Treatments-Medical zonisamide (Zonegran) -good for generalized and partial seizures -long half life topiramate (Topamax) -good for generalized and partial seizures -can cause language delay, cognition -weight loss ethosuximide (Zarontin) -generalized (absence) only
28 Treatments-Medical -lamotrigine (Lamictal) -very good drug for multiple types of seizures -risk of bad rashes even Stevens-Johnson Syn. - start low, go slow -valproic acid (Depakote) -very effective -well known side effects -may be best drug still for many generalized seizures
29 Newer Medications l rufinamide (Banzel) Mechanism:? Sodium channel inactivator Side effects:? l lacosamide (Vimpat) Mechanism:? Sodium channel inactivator Side effects:?
30 Newer Medications l perampanel (Fycompa) Mechanism: AMPA (glutamate) receptor antagonist Side effects: concern for aggression, even homicidal tendencies! l clobazam (Onfi) Mechanism: GABA receptor agonist Side effects: sedation
31 Less commonly used older medications l phenobarbital l phenytoin (Dilantin) l carbamazepine (Tegretol) l felbatol (Felbamate) l tiagabine (Gabatril)
32 Ketogenic diet -Ancient treatment -Modern revival 1980 s *(Atkins and South Beach) -Appeals to some as natural -Still need to recognize side effects and problems like any intervention -Many patients respond, food refusal can be an issue -Mechanism of action unclear
33 Ketogenic Diet (4:1 fat: (protein/carbs) Breakfast: 28 g egg, 11 g bacon, 37 g of 36% heavy whipping cream, 23 g butter and 9 g apple. Snack: 6 g peanut butter and 9 g butter. Lunch: 28 g tuna fish, 30 g mayonnaise, 10 g celery, 36 g of 36% heavy whipping cream and 15 g lettuce. Snack: 18 g of 36% heavy whipping cream, 17 g sour cream, 4 g strawberries and artificial sweetener. Dinner: 22 g minced (ground) beef, 10 g American cheese, 26 g butter, 38 g cream, 10 g lettuce and 11 g green beans..
34 Alternative/Complementary Therapies
35 Cannabinoid Oil (CBD) llegal in TN, illegal Federal Law ltn Law Have epilepsy Be resident of TN Use CBD with <0.9% THC lside Effects minimal ldrug interactions Clobazam levels increased, maybe others
36 Treatments-Surgical -Some patients have seizures from one defined area -Medications ineffective -Many tests done to determine area of seizure origin and whether other important regions are nearby (is surgery going to be effective and safe?)
37 Left Hemisphere Primary Motor Cortex
38 Vagal Nerve Stimulation lfda approved l open loop intermittent stimulation, does not detect seizures lsimilar efficacy as adding a new drug lno drowsy side effects Advantages: Not a medicine, no major side effects, magnet mode -Disadvantages Surgery, expensive, may not work
39 Vanderbilt New Onset Seizure Clinic
40 Problem lchildren with neurological problems need to be seen quickly! Scared families Medical necessity Worried PCP loutpatient clinics have a long wait time led and inpatient admission usually not best forum
41 Who? lfirst time seizure lcomplicated febrile seizure Focal and/or prolonged lbreath holding spells/syncope (few please) lexclusion Criteria Already on anti-seizure medications (unless just started) Has a neurologist
42 Clinic Structure lseveral slots for new patients held each week leeg also available same day lstaffing Melanie Franklin, NP Epilepsy specialists as back-up lcontacting Us
43 Questions?
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