Update in Pediatric Epilepsy

Transcription

1 Update in Pediatric Epilepsy Cherie Herren, MD Assistant Professor OUHSC, Department of Neurology September 20, 2018

2 Disclosures None

3 Objectives 1. Identify common pediatric epilepsy syndromes 2. Describe diagnostic evaluations for new onset seizures 3. Describe treatment options in pediatric epilepsy

4 Definitions Seizure: the clinical manifestation of an abnormal and excessive synchronization of a population of cortical neurons Epilepsy: two or more recurrent seizures unprovoked by any systemic or acute neurological insult Therefore, not all seizures are epilepsy

5 Causes of acute provoked seizures Fever (age 6 months to 6 years) Infection Acute head trauma Hypoglycemia Hyponatremia/hypocalcemia/hypomagnesium Renal failure Hyperthyroidism Cerebral anoxia Alcohol/benzodiazepine withdrawal Drug toxicity/intoxication OU Neurology

6 Normal CNS function Excitation Inhibition glutamate, aspartate GABA

7 Hyperexcitability reflects both increased excitation and decreased inhibition glutamate, aspartate Excitation Inhibition GABA

8 Epidemiology Seizures Incidence: 80/100,000 per year Lifetime incidence: 9% Epilepsy Incidence: 45/100,000 per year Cumulative lifetime incidence: 3% 1% of entire US population

9 Etiology of epilepsy Idiopathic (genetic) Congenital Trauma Ages <15 Ages Vascular Tumor Infection Degenerative Ages Ages >64

10 ILAE classification of seizures Seizures Simple Partial Complex Partial Secondarily Generalized Partial Generalized Absence Myoclonic Atonic Tonic Tonic-Clonic

11 Generalized seizure OU Neurology

12 Partial seizure OU Neurology

13 Evaluation of a first seizure History (witnesses) Physical/neurological examination Blood tests: CBC, electrolytes, glucose, calcium, magnesium, phosphate, hepatic and renal function Lumbar puncture Only if meningitis or encephalitis suspected Blood or urine screen for drugs Electroencephalogram (EEG) CT or MRI brain scan Screen for inborn errors of metabolism (<12 months) OU Neurology

14 Electroencephalogram (EEG) EEG is the most important neurophysiological study for the diagnosis, prognosis, and treatment of epilepsy Graphical depiction of cortical electrical activity, usually recorded from the scalp Abnormal findings consistent with epilepsy are called epileptiform activity and include spikes and sharp waves Activation procedures (sleep deprivation, photic stimulation, hyperventilation)

15 EEG OU Neurology

16 Normal Background OU Neurology

17 MRI Brain OU Neurology

18 Seizures and Epilepsy Seizure Simple Febrile Seizures Complex Febrile Seizures Epilepsy Syndromes Childhood Absence Epilepsy Juvenile Myoclonic Epilepsy Benign Rolandic Epilepsy Infantile Spasms

19 Simple febrile seizures Occur in children 6 months to 5 years Neurologically normal children 1 in 24 hours Last <15 minutes GTC No work-up or treatment typically 3% chance of developing epilepsy

20 Complex febrile seizure Complex febrile seizures occur in neurologically normal children 6 months to 5 years Multiple in 24 hours Prolonged Focal May get EEG or MRI Could consider treating based on results

21 Childhood Absence Epilepsy Previously called petit mal Onset between 4-10 years Normal developmental and neurologic exam Multiple staring spells per day lasting ~15 seconds Thought to be genetic (inheritance is unknown) Rare generalized tonic clonic seizures Frequently outgrow seizures 755o

22 Absence Epilepsy 3 Hz generalized spike and wave discharges

23 Absence Epilepsy Treatment Ethosuximide Valproic Acid Lamotrigine Topiramate Zonisamide AVOID carbamazepine, oxcarbazepine, Phenytoin

24 Juvenile Myoclonic Epilepsy Onset years May evolve from childhood absence Myoclonic seizures, quick jerks often of the arms More common in the morning and after sleep deprivation Photosensitive Precipitated by alcohol Often have generalized tonic clonic seizures also

25 Juvenile Myoclonic Epilepsy 4-6 Hz generalized spike/ polyspike and wave discharges

26 Juvenile Myoclonic Epilepsy Treatment Levetiracetam Valproic Acid Lamotrigine Topiramate Zonisamide AVOID carbamazepine, oxcarbazepine, Phenytoin

27 Benign rolandic epilepsy (BECTS) Most common epilepsy syndrome in children Onset 3-13 years Normal development and neurologic exam Most outgrow by age years Semiology Unilateral facial sensorimotor symptoms (30% of patients) Oropharyngolaryngeal manifestations (53% of patients) Speech arrest (40% of patients), Hypersalivation (30% of patients) Hemiconvulsion/GTC (50%) Likely genetic Confirmed by centrotemporal spikes on EEG Oxcarbazepine considered first line treatment OU Neurology

28 West syndrome Infantile spasms: onset in 1 st year of life Cognitive impairment Hypsarrythmia Etiology: 61-80% 1-2 known cause Hypoxic ischemic encephalopathy (HIE) Chromosomal (Trisomy 21) Congenital brain malformations Ischemic stroke Tuberous sclerosis Peri-ventricular leukomalacia (PVL) Hemorrhage 1. Osborne, J.P., et al (2010). The underlying etiology of infantile spasms (West syndrome): Information from the United Kingdom Infantile Spasms Study (UKISS) on contemporary causes and their classification. Epilepsia: 51(10):

29 Case 1- EEG- Hypsarrythmia OU Neurology

30 West syndrome- Treatment and Outcome Treatment options ACTH vs oral steroids, Vigabatrin Ketogenic diet, Epilepsy surgery 60% epilepsy - ~1/3 evolve to Lennox Gastaut Syndrome 75% developmental delay Lagae, L. et al (2010). Treatment and long term outcome in West syndrome: The clinical reality. A multicentre follow up study. Seizure: Apr;19(3): OU Neurology

31 Epilepsy Treatment Medications Medications Medications Alternative treatments Epilepsy surgery Ketogenic diet Vagal nerve stimulator CBD oil

32 Epilepsy Treatment Medication: Antiepileptic drugs (AEDs) are first line for majority of patients Refractory epilepsy: patients who have failed >2 medications AEDs: Levetiracetam (Keppra): broad spectrum Valproic Acid (Depakote): broad spectrum Topiramate (Topamax): broad spectrum Lamotrigine (Lamictal): broad spectrum Zonisamide (Zonegran): broad spectrum Oxcarbazepine/Carbamazepine (Trileptal/Tegretol): avoid in primary generalized epilepsy Phenytoin (Dilantin): avoid in primary generalized epilepsy Phenobarbital: Used primarily in infants Ethosuximide (Zarontin): Used for absence only Newer AEDs: Clobazam (Onfi), Rufinamide (Banzel), Lacosamide (Vimpat) OU Neurology

33 Success with Anti-epileptic Drug (AED) Regimens

34 Treatment - Epilepsy Surgery OU Neurology

35 SPECT Semiology EEG PET MRI

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37 EEG OU Neurology

38 MRI Brain PET Scan SPECT Scan

39 Neuropsych testing Helps to identify cognitive areas of the brain that aren t functioning well Can help to identify potential areas where seizures are originating Ex. Verbal memory problems may suggest left temporal dysfunction

40 Engel Classification Class Ia: completely seizure-free Class I: seizure-free or auras only or convulsions with drug withdrawal only Class II rare seizures (90% seizure reduction) Class III: reduction of seizure frequency >75% Class IV: reduction of seizure frequency <75% Engel J, Rasmussen TB. Outcome with respect to seizures. 1993: OU Neurology

41 Outcomes Etiology- % seizure free Tumor 80.2% Cortical dysplasia 62.9% Hippocampal sclerosis 81.8% Vascular 75.9% Neurocutaneous 83.3 Other 54.5% Location Temporal 79.5% Frontal 58.8% Parietal 75.0% Occipital 75.0% Surgery type- % seizure free Lobar 74.7% Multilobar 38.5 Hemispherectomy 81.0% OU Neurology

42 Ketogenic diet Special diet for patients with intractable epilepsy High fat low carb diet Must be started in the hospital to monitor glucose and other side effects

43 Ketogenic diet Cream Fat Fruit or vegetable Protein NO bread, pasta, grains, cereal NO sugar or sweets NO starchy fruit or vegetables (corn, peas, potatoes) No juice or milk, no regular sodas Vigilant exclusion/monitoring

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45 Ketogenic diet- side effects Acidosis Constipation Hyperlipidemia Hypoproteinemia Kidney stones Osteoporosis Decreased growth Pancreatitis Hepatitis

46 Ketogenic diet- Efficacy OU Neurology

47 Epilepsy Treatment- VNS Vagal Nerve Stimulator: Implanted device sends electrical pulse to vagus nerve About 1/3 of patients have had the number of their seizures reduced by half or more; less than 5% of patients become seizure free About 1/3 have shown benefit but have had their seizure frequency reduced by less than half About 1/3 have had no worthwhile benefit Side effects: cough, hoarseness

48 CBD Oil Cannabadiol (CBD)- non-psychoactive chemical in the cannabis plant Legal in Oklahoma for families to acquire for intractable epilepsy Exact antiepileptic mechanism unknown but may act on receptors in the hippocampus Studies show 50-60% reduction in seizures in difficult to treat epilepsy (children and adults) No placebo control May interfere with metabolism of other medications No specific diagnoses respond better Side Effects- sedation, nausea, vomiting, elevated liver enzymes, behavioral problems, insomnia OU Neurology

49 Take home points Epilepsy has a variable presentation and prognosis Categorizing patients into epilepsy syndromes can help determine etiology, best treatment options and prognosis Identifying patients who may benefit from non-medication options is important early to minimize morbidity

50 Questions?????? OU Neurology