1. PEDIATRIC PROTOCOLS Elana Pinchefsky, PGY-2 August 1 st, 2012

2. Outline  Protocols for:  Seizures  Headaches and migraines  Tics and tourette syndrome  Therapeutic hypothermia

3. Seizures

4. Febrile Seizures SimpleAtypical/Complex (25-30%) GeneralizedFocal Brief <15 minutes Prolonged >15 minutes (status epilepticus) Isolated 1 seizure/24 hrs Multiple > 1 seizure/24 hrs Normal development & neurological exam Abnormal neurodevelopment before seizure Classification :

5. Febrile Seizures  Occur in 3-5% of children  Between 6 months – 6 years  peak age 18-24 months  Antipyretics make the child more comfortable, they do not prevent recurrent FS  High recurrence: 1/3  1/2 if less that 1 y.o.  10% of children experience  3 febrile seizures  Factors that increase risk of recurrence: Young age at time of first febrile seizure (<18months) Family Hx of febrile seizures Relatively lower fever at the time of the initial seizure Short duration of fever before the initial seizure (<1 hr) Complex features

6. Febrile Seizures  Risk of developing epilepsy in general population: 1/200  If simple febrile seizures 1/100   risk of epilepsy if: Complex features Neurodevelopmental abnormality before the first seizure Family history of afebrile seizures Short duration (<1 hour) of fever before seizure  Risk of epilepsy increased with the presence of each atypical feature:  1 atypical feature – 3%  2 atypical features – 6%  3 atypical features – 9%  4 atypical features – 12-15%

7. Febrile Seizures Febrile Seizures. BMJ. 2007

8. Febrile Status Epilepticus  5% of all cases of febrile seizures  25% of all childhood cases of status epilepticus  More likely to have focal features  Compared with afebrile SE – does Not lead to new death or disability  Association with MTS and MTLE  No causal data  Treatment similar to SE,  generally rapid response to Tx  Ismail et al. Saint-Justine (2012, article in press)  Phenytoin is rarely effective in controlling febrile SE Phenytoin alone was effective in treating only 14.5% of FSE (but 45% nonevaluable) 40% did not respond to Dilantin Sz duration was 2x longer when phenytoin failed (52.8 vs 109.9 min)  Sodium channel mutations (SCN1A) have been linked to atypical febrile sz  may limit efficacy of Na channel blockers

10. First non-febrile seizure  Syncope  Daydreaming  Breath-holding spells (18 mo – 4 yrs)  GERD  Movement disorders (tics)  Sleep disorders  Migraine and migraine equivalents  Vestibular disorders, benign paroxysmal vertigo  Psychotic hallucinations and delusions  Nonepileptic events (pseudoseizures)  Panic attacks  Transient ischemic events  Transient global amnesia  …  Provoked?  Electrolyte abnormalities  Infection (meningitis)  Trauma  Toxic ingestion  Vasculitis  Inborn error of metabolism  CNS tumour  Unprovoked  Childhood epilepsy syndromes Is it a seizure? - dDx Yes

13. Status Epilepticus  Established SE: a seizure lasting longer than 30 minutes or a series of seizures without a return to baseline level of alertness between the sz.  Early SE: 5 - 30min  Refractory SE: Sz that persists (>60min) despite tx with adequate doses of initial 2 or 3 AEDs.  10-25% of children with epilepsy may eventually develop SE  16% with first episode SE will have a recurrence within 1 yr.

14. Status Epilepticus  Lambrechtsen et al. (2008)  Sz were terminated by a 3 rd AED in 100% when administered within 60 min of the 1 st AED Only 22% if >1hour after the initial AED  If 3 rd AED within an hr of Tx initiation – return to baseline significantly more often than when delayed (81% vs. 0%)

15. Status Epilepticus  ABCs, O 2, glucose, temperature, monitors, IVs, labs (CBC, CBG, electrolytes, Ca, Mg, PO 4, BUN/Cr, LFTs, AED levels).  Consider toxicology, blood cultures, CT head, LP.  Initial management  Benzodiazepines (effective in 30-40%) Midazolam IV/IN/IM 0.15 mg/kg. Max 10 mg Lorazepam IV/PR 0.1 mg/kg. Max 8 mg/12h or 0.1 mg/kg/12h IV/PR Repeat q5 min. x 2 PRN  If ongoing seizure  Phenytoin 20mg/kg IV/IO. Max 1000mg

16. Status Epilepticus  Second-line management  Phenytoin 10mg/kg IV/IO. Max 1000mg Repeat x 1 PRN  If ongoing seizure – *Consult Neurology and PICU  Third-line management  Phenobarbital IV/IO 20 mg/kg Repeat 10mg/kg IV/IO x 2 PRN  Valproate Acid, Levetiracetam IV

17. Status Epilepticus  Fourth-line management  Ideally in PICU under EEG monitoring  Midazolam infusion Initial 0.15mg/kg then 1-2 mcg/kg/min titrated every 15 minutes to produce seizure control on EEG for minimum 12-48 hrs  Phenobarbital infusion Initial 5mg/kg then 1-5mg/kg/hr. Additional doses to produce burst-suppression on EEG for minimum 4 hours  Pentobarbital, propofol, ketamine  If < 2 y.o. – consider Pyridoxine 100 mg IV push  If ongoing seizure  General anaesthesia – Isoflurane  Ketogenic diet, hypothermia, surgery, immune modulating therapy

19. Headaches and Migraines

20. Migraines  Prevalence:  3 to 7 years 1 to 3 % ♂ > ♀  7 to 11 years 4 to 11% ♂ = ♀  > 15 years 8 to 23% ♀ > ♂  Peak Incidence:  Migraine with aura ♀ : 12-13 yo (14/1000 person-yrs) ♂ : 5 yo (6.6/1000 person- yrs)  Migraine without aura ♀ 14-17 yo (19/1000 person-yrs) ♂ : 10-11 yo (10/1000 person- yrs) After age 10 ♀ > ♂ (~puberty) After age 10 ♀ > ♂ (~puberty)

21. Migraine Classification – ICHD II

22. Migraines  Migraine without aura – (60-85%)  most frequent  Migraine with aura – (15-30%)  Typical aura: visual disturbances, distortions or obscuration before or as the headache begins that start gradually and last for several minutes Binocular visual impairment w/ scotoma (77%) Distortions or hallucinations (16%) Monocular visual impairment or scotoma (7%)  Sudden images and complicated visual perceptions  r/o benign occipital epilepsy  Rare in children:  Typical aura with nonmigraine headache  Typical aura without headache

23. Diagnostic Criteria  Pediatric Migraine without aura – IHS 2005 A) At least 5 attacks fulfilling criteria B through D B) Lasting 1 to 72 hours C) At least 2 of the following: Unilateral or bilateral frontotemporal (not occipital) Pulsating quality Moderate or severe pain intensity Aggravation by or causing avoidance of routine physical activity D) During the headache, at least 1 of the following Nausea and/or vomiting Photophobia and phonophobia, which may be inferred from behavior E) Not attributed to another disorder

24. Diagnostic Criteria  Pediatric Migraine with aura – IHS 2005 A) At least 2 attacks fulfilling criteria B through D B) Aura consisting of at least one of the following, but no motor weakness: 1. fully reversible visual symptoms including positive features (eg, flickering lights, spots or lines) and/or negative features (ie, loss of vision) 2. fully reversible sensory symptoms including positive features (ie, pins and needles) and/or negative features (ie, numbness) 3. fully reversible dysphasic speech disturbance C) At least two of the following: 1. homonymous visual symptoms and/or unilateral sensory symptoms 2. at least one aura symptom develops gradually over  5 minutes and/or different aura symptoms occur in succession over  5 minutes 3. each symptom lasts  5 and  60 minutes D) Headache fulfilling criteria B-D for 1.1 Migraine without aura begins during the aura or follows aura within 60 minutes E) Not attributed to another disorder

25. Migraines  Basilar-type Migraine – (3-19%)  Mean age of onset 7 y.o.  Episodes of dizziness, vertigo, visual disturbance, ataxia, or diplopia, followed by the headache  The pain may be occipital  Diagnostic criteria require ≥2 Sx and emphasize bulbar and bilateral sensorimotor features

26. Migraines  Familial Hemiplegic Migraine  Autosomal dominant  3 known loci: CACNA1A (FHM1), chr 19 ATP1A2 (FHM2), chr 1 SCN1A (FHM3), chr 2  Aura that has “stroke-like” qualities  some degree of hemiparesis  Focal neuro deficits precede HA by 30-60 minutes, but occasionally extend well beyond the headache itself (up to 24hrs)  HA often contralateral to focal deficits

27. Migraine Equivalents – precursors of migraines  Benign paroxysmal torticollis  Onset during infancy (2-8 mo.)  Rare paroxysmal movement d/o or dyskinesia  Attacks of head tilt alone or with V° & ataxia, lasting hrs to days  Other dystonic features: truncal or pelvic posturing  Benign paraxysmal vertigo  Onset in young children  Abrupt and brief episodes (minutes to hrs) of unexplained unsteadiness or ataxia  Clusters that typically resolve with sleep  Cyclic vomiting syndrome  Onset during childhood (~ 5 y.o.) ♂ = ♀  Recurrent episodes of intense vomiting w/ intervening wellness  Recognizable by their stereotypical time of onset, duration and symptomatology  Regular q 2-4 wks, last 1-2 days, start in early morning  Abdominal migraine  Onset in school-age children  Episodic moderate-to-severe intensity vague, midline or periumbilical, abdo pain lasting 1 to 72 hours associated with vasomotor symptoms (flushing, pallor) and N/V

28. Diagnostic Criteria

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35. Tics and Tourette Syndrome

36.  Tics:  Stereoyped, intermittent, sudden, discrete, repetitive, nonrhythmic movements, most frequently involving head and upper body  Transient (1-12 months) or chronic (>12 mo)  Transient motor tics in 25% of children  Tourette Syndrome: (1%, ♂ > ♀ )  Diagnostic criteria from DSM-IV-TR: Both multiple motor and one or more vocal tics must be present at some time during the illness, although not necessarily concurrently The tics occur many times a day (usually in bouts) nearly every day or intermittently over more than 1 year, during which time there must not have been a tic-free period of more than 3 consecutive months The age at onset is younger than 18 years The disturbance is not due to the direct physiological effects of a substance (eg, stimulants) or a general medical condition (eg, Huntington disease or postviral encephalitis)

37. Tics and Tourette Syndrome

40. Therapeutic Hypothermia

41.  Standard of care for infants with moderate to severe HIE  Whole body cooling vs selective head cooling  Started before 6 hours of life - Before the secondary phase of energy failure  During 72 hours -until the end of the secondary phase of energy failure (48-72hrs)  At 33.5° (34° ± 0.5°)  Amplitude-integrated EEG

42. Criteria for Cooling  ≥36 wks and ≥1800g  Cord pH ≤7.0 or base excess ≥-16mEq/L  First hour of life CBG with pH ≤7.0 or base excess ≥- 16mEq/L  Perinatal history of an event such as: placental abruption, cord prolapse, fetal bradycardia, shoulder dystocia…  Need for resucitation or ventilation >10 minutes after birth  Apgar ≤5 at 10 minutes  Convulsions  Clinical signs of HIE

43. Criteria for Therapeutic Hypothermia - Should I cool this baby?

44. HIE clinical evaluation

45. Predictors of Outcome 1. Severity of the neonatal encephalopathy 2. Temporal evolution in clinical status over the first week of life 3. Presence of refractory neonatal seizures 4. Burst-suppression EEG pattern 5. Qualitative impression of the severity of EEG changes

46. Thank You

47. References  Ahmad et al. Febrile Status Epilepticus: Current State of Clinical and Basic Research. Semin Pediatr Neurol. 17:150-154. 2010  Pediatrics In Review. Febrile Seizures. Vol. 18 No. 1 January 1, 1997 pp. 5 -9.  Sadleir et al. Febrile seizures. BMJ. 2007 February 10; 334(7588): 307–311.  Ismail et al. Lack of efficacy of phenytoin in children presenting with febrile status epilepticus. American Journal of Emergency Medicine. 2012 article in press.  Lambrechtsen et al. Aborted and refractory status epilepticus in children: A comparative analysis. Epilepsia. Vol 49, issue 4, p. 615-625, April 2008.  Abend et al. Medical Treatment of Pediatric Status Epilepticus. Seminars in Pediatric Neurology 17:169-175. 2010.  IHS guidelines. http://www.ihs- headache.org/ihs_v3/user/code_public/guidelines_frame_access.asp?Allow=0&idSource=1  Stewart et al. Age- and Sex-specific Incidence Rates of Migraine with and without Visual Aura. Am. J. Epidemiol. (1991) 134 (10): 1111-1120.  Lewis D.W. Pediatric Migraine. Pediatrics In Review. Vol. 28 No. 2 February 1, 2007 pp. 43 - 53.  H. Zinner and Jonathan W. Movement Disorders I: Tics and Stereotypies. Pediatrics in Review 2010; 31:223-233