Seizures: Nuts and Bolts National Pediatric Nighttime Curriculum Written by Anna Lin, MD Lucile Packard Children’s Hospital

Learning Objectives Understand the importance of initial assessment of patients who have seizures Be able to initiate treatment for patients who have seizures Know alternatives to first line treatments for status epilepticus

Case #1 14-month-old developmentally normal boy who presents with generalized tonic-clonic seizures associated with fever. How would you initiate management? What other information would be useful to you as you are starting to intervene? What type of work-up does this patient need? Always start with ABCs Consider: How long has the seizure been going on? How has the patient’s behavior been prior to the event? Are there other symptoms? Has he ever done this before? Is he developmentally normal? Is there a family history of febrile seizures? Review AAP guidelines on febrile seizures: PEDIATRICS Volume 127, Number 2, February 2011 If this is a simple febrile seizure (< 15 minutes, no focality, < 2 in 24 hours), then no further work-up is necessary. CBC with diff, electrolyte panels do not need to be performed as routine work-up for febrile seizures. If the patient is ill-appearing or has meningeal signs, perform an LP. If the patient is 6-12 months and under-immunized or not immunized, consider LP. If the patient is pretreated with antibiotics, consider LP.

Case # 2 12-year-old boy with obstructive hydrocephalus and VP shunt who presents with generalized tonic-clonic seizures for the past 15 minutes. How would you initiate management? What other information would be useful to you as you are starting to intervene? What type of work-up does this patient need? Always start with ABCs. Use benzodiazepines. Consider loading with anti-epileptics. Consider: Does this patient have a seizure disorder? If so, when was the last time he had a seizure? Is this the same type of seizure? Does he take any anti-epileptic medications? Has he missed any doses? How has his behavior been prior to the seizures? Have there been other symptoms? Vomiting may be indicative of increased ICP. Fever could signal shunt infection. When was the patient’s VP shunt last evaluated? Was it recently revised? Ask what type of physical assessment this patient should have. This is an option: Patient will be bradycardic with hypertension (the start of Cushing’s triad) We want a pupillary exam after ABCs have been taken care of. The left pupil will be fixed and dilated. Lead a discussion into the underlying problem to help ameliorate the seizures  increased ICP/shunt malfunction  how do we treat increased ICP? Treatment for increased ICP  elevate HOB, hyperventilate (if the patient is intubated), mannitol, hypertonic saline, make the body hypothermic Pediatric Critical Care Medicine 4(30):Supplemental, 2003.

Types of Seizure Partial Seizures Generalized Seizures Simple vs. Complex Different types (motor, sensory, autonomic, “psychic”) Generalized Seizures Convulsive vs. Nonconvulsive Secondarily generalized vs. Secondary Partial Seizures Simple vs. complex – Is consciousness maintained? Is there laterality? Types of partial seizures Motor – focal motor activity, Jacksonian march, versive movements (turning of the eyes, head and/or trunk), vocalizations or arrest of speech Sensory – paresthesias, feelings of distortion of an extremity, gustatory sensation, olfactory symptom, auditory symptoms, visual phenomena (flashing lights) Autonomic seizures – sweating, piloerection, papillary changes, epigastric “rising” sensation Psychic symptoms – dysphagia, cognitive, déjà-vu (dysmnestic), affective, illusions, hallucinations Generalized Seizures Generally bilateral, involving both hemispheres. No awareness. Convulsive vs. nonconvulsive (absence seizures) Secondary vs secondarily generalized seizures Secondary suggests underlying etiology – CNS insult (not genetic or idiopathic) Eg seizure due to HIE Secondarily suggests initial focality Eg benign rolandic epilepsy

Status Epilepticus A patient is in status epilepticus if seizure activity has lasted > 30 minutes or there are multiple seizure episodes with failure to regain consciousness between episodes This is an arbitrary definition In children with SE lasting > 30 minutes, associated with mortality ~ 20% Seizures > 5 minutes will have a high risk of lasting 30 minutes or more Childhood status incidence 17-23/100,000/yr, febrile SE most common 60% neurologically normal prior to SE Neurologic sequelae Encephalopathy in 6-15% Neurologic deficits in 9-11% Risk factors for status epilepticus History of epilepsy SE as first presentation/history of prior SE Partial seizures that tend to cluster Focal background EEG abnormalities Generalized abnormalities on neuroimaging Younger age at onset (< 12 months) Symptomatic etiology of epilepsy

Management of Seizures Initial assessment Airway Breathing Circulation Call for help Hospitalist Neuro PICU/RRT Ask for more history How long has the patient been seizing? New-onset vs. known seizure disorder Baseline seizure frequency, is this typical or not? Events leading up to this episode Meds/triggers History of status Describe the episode What happened? Was there focality? What was moving and how was it moving? Were there other symptoms? Color? How long did the episode last? Setting in which the seizure occurs Nocturnal? Medications? Illness/fever? What happened before the event? Precipitants? Headache, anorexia, nausea, vomiting, breath-holding? Certain activities? Aura? What happened after the event? Immediate recovery? Confusion/somnolence? How long did this last? Ability to speak/follow commands? Not moving limbs? Other important tidbits – Has the patient had these episodes before? What has been done to evaluate/treat these episodes? How many? How often? Has the patient ever been in status epilepticus? Normal development? Social stressors? Previous history of neurological illness (infection, HIE, trauma)? Drug use? (especially in adolescents) FAMILY HISTORY!!!!! Seizure, developmental delay , genetic/metabolic problems, consanguinuity

Management of Seizures Consider rapid work-up for underlying etiologies CNS infection Acute HIE Metabolic disease Electrolyte imbalance TBI Drugs, intoxications, poisonings Cerebrovascular event

Benzodiazepines Lorazepam (Ativan) Midazolam (Versed) 0.05-0.1 mg/kg IV q10-15 min, max dose 4 mg Less respiratory depression than diazepam, longer duration of action, slower onset (2 min) Midazolam (Versed) 0.15 mg/kg IV then continuous infusion of 1 mcg/kg/min Other formulations available: IM, buccal, intranasal, oral, and rectal Short half life, faster onset (1 min)

Benzodiazepines (2) Diazepam (Valium) 0.05-0.3 mg/kg IV q15-30 min, max dose 10 mg Quick onset (10-20 sec), rectal formulation, higher risk of respiratory depression Not considered first line Lower efficacy Increased respiratory depression

Fosphenytoin/Phenytoin Fosphenytoin (Cerebyx) 15-20 mg PE/kg IV/IM, may infuse 3 mg/kg/min (max 150 mg/min), max dose 1500 mg PE/24 hours Prodrug of phenytoin which has fewer side effects Can cause cardiac arrhythmias Avoid for status with myoclonic seizures or absence seizures Consider alternatives in seizures associated with illicit drug use Phenytoin (Dilantin) Not used first line as there are many side effects Cardiac arrhythmias/hypotension associated with propylene glycol used to dissolve phenytoin Local pain, venous thrombosis and purple glove syndrome  skin necrosis, limb ischemia  amputation

Barbiturates Phenobarbital (Luminal) Pentobarbital (Nembutal) 15-20 mg/kg IV/IM, may repeat 5 mg/kg IV q15-30 min, max dose 40 mg/kg Prolonged sedation, respiratory depression, hypotension Generally used after failure of benzodiazepines and fosphenytoin Pentobarbital (Nembutal) 12 mg/kg IV followed by 5 mg/kg/hr infusion Titrate to EEG inactivity Used for refractory status epilepticus

Other agents Propofol (Diprivan) Rapid onset, short duration of action Mechanism of action is unclear Hypotension, apnea and bradycardia are common Intubation and ventilation are required for the use of this medication Prolonged use can result in hypertriglyceridemia and pulmonary edema Associated with fatal acidosis and rhabdomyolysis

Other agents (2) AEDs with some data to suggest use in refractory SE Valproic acid (Depakote): not yet approved for SE, some data to support its use Topiramate (Topamax): PO only Levetiracetam (Keppra): adult data only

References AAP Subcommittee on Febrile Seizures. Clinical Practice Guideline—Neurodiagnostic Evaluation of the Child With a Simple Febrile Seizure. Pediatrics 2011, 127(2): 389-394 Singh RK, Gaillard WD. Status Epilepticus in Children. Current Neurology and Neuroscience Reports 2009, 9:137–144 Wilfong A. Overview of the classification, etiology, and clinical features of pediatric seizures and epilepsy. Up To Date, 2011.

Questions 1. You are paged by the nurse to come to the bedside of a patient with known seizure disorder who is actively seizing. On arrival to the bedside, you note that the patient is having tonic-clonic movements of all extremities, upward eye deviation, and frothing at the mouth. The next step in the assessment/management of this patient is to A.Ask the nurse how long the patient has been seizing B.Wait for your senior resident to come and assist you C.Have the nurse give lorazepam through the IV D.Suction and secure the airway E.Obtain a fingerstick blood glucose

Questions D.Suction and secure the airway In all patients, the first assessment you make should be checking airway, breathing and circulation. Although you should call for help, you do not need to wait to start life-saving interventions. While lorazepam is an excellent anti-seizure medication, if your airway is not secure, you could risk putting this patient into respiratory failure. Asking for more information can be helpful in overall management, but is not the next best step. You can consider hypoglycemia as an underlying etiology, but this is also not the first step in your assessment.

Questions 2.You are called to the Emergency Department to admit a 2-year-old patient who had a 2 minute generalized tonic-clonic seizure associated with fever. The patient is well-appearing and at baseline neurological status 30 minutes after the event. His neurological examination is normal. What should you do? A.Discharge the patient home after seizure education. B.Admit the patient to the floor for overnight observation. C.Recommend the Emergency Department obtain a head CT. D.Obtain screening labs including a CBCD, chemistry panel and CRP. E.Discharge the patient home with rectal diazepam.

Questions A.Discharge the patient home after seizure education. This patient has had a simple febrile seizure. The general course of this disease process is benign. It needs no further work-up. Use of anti-epileptic medications is not indicated in simple febrile seizures. Admission is not necessary. Parents should be reassured about this incident and given education about recurrence risk and when to activate the emergency medical system (i.e. call 911).

Questions 3. All the following medications are used to treat status epilepticus EXCEPT A.Lorazepam B.Fosphenytoin C.Phenobarbital D.Propofol E.Levetiracetam

Questions E.Levetiracetam Levetiracetam (Keppra) is not routinely used to treat status epilepticus. Although there is some adult data to support its use, its use in pediatrics is not widespread. Other medications which are not routinely used in the treatment of status epilepticus in the pediatric population include valproic acid and topiramate. These medications may be used in refractory status epilepticus.

Questions 4. A 3-year-old boy with known seizure disorder is being admitted for increased seizure frequency. As you assess the patient, he develops generalized tonic-clonic seizures. He is maintaining his airway and oxygen saturation is 94% on RA. He is afebrile. He does not have IV access. What would you do next? A.Administer buccal midazolam. B.Order an emergent head CT. C.Check electrolytes and glucose STAT. D.Obtain more history. E.Start a peripheral IV.

Questions D.Obtain more history. Since there is no vital sign instability, the patient does not require immediate treatment. This seizure may represent be typical for him. Important history to obtain includes frequency and type of seizures, medication history (what type of anti-epileptic therapy is the patient on and how often does he take it, has he missed any doses), any triggers for seizures/new exposures, previous history of status epilepticus and other recent events or symptoms. Administration of buccal midazolam is not indicated if the seizure normally resolves within a few minutes. The patient may require further brain imaging. In a patient with known seizure disorder and no history of trauma or increased ICP, emergent head CT may expose the patient unnecessarily to high doses of radiation. MRI of the brain may the imaging modality of choice, but does not need to be performed emergently. Starting a peripheral IV and checking labs could be useful but are not the next steps in the evaluation of this patient.

Questions 5.Which of the following is TRUE about fosphenytoin/phenytoin? A.Phenytoin is used first-line in status epilepticus. B.Phenytoin can cause cardiac arrhythmia, but fosphenytoin does not. C.The loading dose of fosphenytoin is 20 mg/kg PE IV or IM. D.Fosphenytoin is best used for patients with myoclonic or absence seizures. E.Phenytoin is a prodrug.

Questions C.The loading dose of fosphenytoin is 20 mg/kg PE IV or IM. Fosphenytoin is ordered in mg PE (phenytoin equivalents). It is a prodrug which is converted into phenytoin. It can cause cardiac arrhythmias although less commonly than phenytoin. Phenytoin should be avoided in patients with myoclonic or absence status epilepticus. Phenytoin is not used first-line because of its cardiac arrhythmias and risk of venous thrombosis.