1. Pediatric Emergency Conference Guanzon Guerrero Guerzon Guevarra Guinto Gutierrez Hermoso Icasas Ignacio

2. General Data Michael 3 week old male Chief complaint: seizures

3. History of Present Illness: Gestational and Birth History: 25 year old primigravid Unremarkable prenatal and birth history CS - due to CPD BW: 2.8 kg Spontaneous cry and respiration Nursery Stay: 3 days Newborn screening: Positive for congenital adrenal hyperplasia - Advised confirmatory test and further work-up but was not able to comply

4. History of Present Illness: 2 days PTC: (+) 5x water stools (+) 3x vomiting of previously ingested food Few hours PTC: - drowsy - generalized tonic-clonic seizures Rushed to the ER

5. Initial assessment at the ER: Was in active seizures afebrile CR: 180 bpm RR: 50-60 cpm Bluish lips

6. Initial management at the ER: Oxygen per mask was administered Diazepam 0.3 mg/kg/dose per IV at 15 mins. Interval for 3 doses (Seizure persisted) Phenobarbital – loading dose

7. Secondary assessment: Unremarkable chest and abdomen (+) hypospadias Penile length: 1.5 cm Darkly pigmented scrotal sac Pulses were full and equal Good capillary refill

8. Laboratory results: Lab testsResultReference Value Na120 K6.0 Hgtlow

9. Salient Features

10. Differential Diagnosis Presenting manifestation: seizure in a neonate Seizure: paroxysmal, time limited change in motor activity and/or behavior that results from abnormal activity in the brain Common in pediatric age group Neonates are at particular risk for the development of seizure Nelson’s textbook of Pediatrics 17 th edition

11. Manifestations of a seizure: Vocal: Cry or gasp, slurring of words, garbled speech Motor: Head or eye turning, eye deviation, posturing, jerking (rhythmic), stiffening, automatisms (purposeless repetitive movements such as picking at clothing, lip smacking); generalized or focal movements Respiration: Change in breathing pattern, cessation of breathing, cyanosis Autonomic: Pupillary dilatation, drooling, change in respiratory or heart rate, incontinence, pallor, vomiting Loss of consciousness or inability to understand or speak Practice parameter: Evaluating a first nonfebrile seizure in children Report of the Quality Standards Subcommittee of the American Academy of Neurology, the Child Neurology Society, and the American Epilepsy Society D. Hirtz, MD; S. Ashwal, MD; A. Berg, PhD; D. Bettis, MD; C. Camfield, MD; P. Camfield, MD; P. Crumrine, MD; R. Elterman, MD; S. Schneider, MD; and S. Shinnar, MD, PhD

12. Seizure Infectious causes: Bacterial Viral Fungal AfebrileFebrile Seizure – like Events Benign Paroxysmal Torticollis of Infancy Breath holding spells: - cyanotic spells - pallid spells Shuddering attacks Night terrors Metabolic disorders Electrolyte imbalance Hypoglycemia Hypoxia Drug related

13. Non-febrile seizure Things to consider: Metabolic: Congenital Adrenal Hyperplasia Electrolyte Imbalance: diarrhea(5X) + vomiting (3x) Hypoxia: bluish lips

14. Seizures result from rapid abnormal electrical discharges from cerebral neurons presents clinically as involuntary alterations of consciousness or motor activity Consumption of oxygen, glucose, and energy substrates (e.g, ATP, phosphocreatine) is significantly increased in cerebral tissue during seizures. Optimal delivery of these metabolic substrates to cerebral tissue requires adequate cardiac output and intravascular fluid volume. Pediatric, Status Epilepticus; emedicine 2008

15. Factors that lower Seizure Threshold Sleep deprivation Hyperventilation Photic stimulation Infection Metabolic disturbances Head trauma Cerebral ischemia Kindling Handbook of Neurosurgery by Greenberg

16. Drugs which can cause seizures Antibiotics ◦ Penicillins ◦ Isoniazid ◦ Metronidazole Anesthetics, narcotics ◦ Halothane, enflurane ◦ Cocaine, fentanyl ◦ Ketamine Psychopharmaceuticals ◦ Antihistamines ◦ Antidepressants ◦ Antipsychotics ◦ Phencyclidine ◦ Tricyclic antidepressants

17. Important points in the History The course of current seizure activity ◦ Time and nature of onset of seizure activity ◦ Involvement of extremities or other body parts ◦ Nature of movements (eg, eye movements, flexion, extension, stiffening of extremities), including any focal movements and details of postictal neurologic deficit ◦ Incontinence ◦ Cyanosis (perioral or facial) ◦ Duration of seizure activity prior to medical attention ◦ Mental status after cessation of seizure activity Fever or intercurrent illnesses Prior history of seizures - If present, specify medications, anticonvulsant use, and compliance. Pediatric, Status Epilepticus; emedicine 2008

18. Important points in the History Head injury (recent and remote) CNS infection or disease (eg, meningitis, neurocutaneous syndrome) Intoxication or toxic exposure Other CNS abnormality (eg, ventricular- peritoneal shunt, prior CNS trauma) Birth history and developmental delay (eg, anoxic encephalopathy, cerebral palsy) Other medical history (eg, acquired immunodeficiency syndrome, systemic lupus erythematosus, type 1 diabetes mellitus) Pediatric, Status Epilepticus; emedicine 2008

19. Important points in the PE Signs of sepsis or meningitis ◦ Temperature more than 38.5°C; in patients younger than 2-3 months, more than 38.0°C ◦ Respiratory distress ◦ Cyanosis ◦ Poor peripheral perfusion ◦ Bulging fontanelles in infant ◦ Meningismus (in children >12-18 mo) ◦ Presence of petechiae or purpura, herpetic vesicles Evidence of head or other CNS injury ◦ Bradycardia, tachypnea, and hypertension (Cushing triad for signs of increased intracranial pressure) ◦ Poor pupillary response ◦ Asymmetry on neurologic examination ◦ Abnormal posturing ◦ Gross deformity or soft tissue injury to head Hallmarks of neurocutaneous syndromes (e.g., port wine stain) Pediatric, Status Epilepticus; emedicine 2008

20. Monitoring of Vital Functions Respiratory rate, blood pressure, cardiac rate Observation of seizure activity Skin bruises, petechiae or needle marks Papilledema, retinal hemorrhages Organomegaly and abdominal tenderness

21. Status Epilepticus Continuous clinical or electroencephalographic seizures lasting for at least 30 minutes or recurrent seizures without return of consciousness during interictal period: the series lasting for 30 minutes or more. It is a medical emergency. Handbook of Medical & Surgical Emergencies, 6 th edition

22. Clinical Classification of Status Epilepticus Overt generalized convulsive status epileptus Subtle generalized convulsive status epilepticus Simple status epilepticus Nonconvulsive status epilepticus Continuous convulsive activity and intermittent convulsive activity without regaining full consciousness Convulsive (tonic-clonic) Tonic Clonic Myoclonic Coma following generalized convulsive status epilepticus with or without motor activity Consciousness preserved Simple motor status epilepticus Sensory status epilepticus Aphasic status epilepticus Consciousness impaired; twilight or fugue state Petit mal status (absence status) Complex partial status epilepticus Handbook of Medical & Surgical Emergencies, 6 th edition

23. Etiologies Febrile seizures Cerebrovascular accidents CNS infection Idiopathic Epilepsy Subtherapeutic antiepileptic drug Electrolyte imbalance Drug intoxication Alcohol withdrawal Traumatic brain injury Anoxia Tumor Handbook of Neurosurgery by Greenberg

24. Neonates (first month of life) Early childhood (<6 y) Children and adolescents (>6 y) Birth injury (eg, anoxia, hemorrhage) and congenital abnormalities Birth injury Metabolic disorders (eg., hypoglycemia, hypocalcemia, hyponatremia) and inborn errors of metabolism (eg., lipidoses, amino acidurias) Febrile convulsions (3 mo to 6 y)Trauma Infection (eg, meningitis)Infection Metabolic disordersEpilepsy with inadequate drug levels TraumaCerebral degenerative disease Neurocutaneous syndromesTumor Cerebral degenerative diseasesToxins TumorsIdiopathic Pediatric, Status Epilepticus; emedicine 2008 DIFFERENTIAL DIAGNOSIS

25. In children < 1year age 75% acute cause 30% electrolyte disorders 28% secondary to CNS infection 19% associated with fever Handbook of Neurosurgery by Greenberg

26. Prolonged seizures are associated with cerebral hypoxia, hypoglycemia, and hypercarbia and with concurrent and progressive lactic and respiratory acidosis. When cerebral metabolic needs exceed available oxygen, glucose, and metabolic substrates (especially during status epilepticus), neuronal destruction can occur and may be irreversible. Hypoxia, hypercarbia, hyperthermia, tachycardia, hypertension, hyperglycemia, hyperkalemia, and lactic acidosis result from massive sympathetic discharge. Pediatric, Status Epilepticus; emedicine 2008

27. Prolonged seizures Duration of seizure Lifethreateningsystemicchanges Death Temporarysystemicchanges Werner, MD; GTC SE in Children; University of Kentucky Hospital

28. Respiratory Hypoxia and hypercarbia ◦ Ventilation  (chest rigidity from muscle spasm) ◦ Hypermetabolism  (  O 2 consumption,  CO 2 production) ◦ Poor handling of secretions Werner, MD; GTC SE in Children; University of Kentucky Hospital

29. Hypoxia Hypoxia/anoxia markedly increase the risk of mortality in SE Seizures (without hypoxia) are much less dangerous than seizures and hypoxia Towne AR. Epilepsia 1994;35(1):27-34

30. Neurogenic Pulmonary Edema Rare complication of SE in children Likely occurs as consequence of marked increase of pulmonary vascular pressure during SE Johnston SC. Postictal pulmonary edema requires pulmonary vascular pressure increases. Epilepsia 1996;37(5):428-32

31. Acidosis Respiratory Lactic ◦ Impaired tissue oxygenation ◦ Increased energy expenditure

32. Hemodynamics Sympathetic overdrive ◦ Massive catecholamine / autonomic discharge ◦ Hypertension ◦ Tachycardia ◦ High CVP Exhaustion  Hypotension  Hypoperfusion Exhaustion  Hypotension  Hypoperfusion 0 min 60 min

33. Cerebral blood flow - Cerebral O 2 requirement Blood pressure Blood flow O 2 requirement Seizure duration HyperdynamicExhaustion Lothman E. Neurology 1990;40(5 Suppl 2):13-23. Hyperdynamic phase ◦ CBF meets CMRO 2 Exhaustion phase ◦ CBF drops as hypotension sets in ◦ Autoregulation exhausted ◦ Neuronal damage ensues

34. Glucose Glucose Seizure duration 30 min SE SE + hypoxia Lothman E. Neurology 1990;40(5 Suppl 2):13-23. Hyperdynamic phase ◦ Hyperglycemia Exhaustion phase ◦ Hypoglycemia develops ◦ Hypoglycemia appears earlier in presence of hypoxia ◦ Neuronal damage ensues

35. Mortality The primary determinant of mortality and morbidity of SE in children is its etiology The greatest mortality and highest rate of neurological deficits occurs when SE is caused by an acute neurological condition (infection, trauma, stroke) Mitchell WG. J Child Neurol 2002;17 Suppl 1:S36-43.

36. Mean duration of SE in patients without neurologic sequelae is 1.5hours. Mortality is lowest among children (~6%) subtherapeutic AEDs unprovoked SE Highest Mortality elderly patients SE due to anoxia or CVA Handbook of Neurosurgery by Greenberg

37. MANAGEMENT

38. Management 1. Control the seizure. 2. Correct the electrolyte imbalance 3. Work-up and treatment of Congenital Adrenal Hyperplasia 4. Anticipatory Guidance

39. General Initial Management of Seizure 1. Assessment and control of the airways and of ventilation, 2. ABG, ECG and blood pressure monitoring. 3. Other measures include: ◦ i.v. glucose and thiamine as required, ◦ emergency measurement of antiepileptic drug levels, electrolytes and magnesium, ◦ a full haematological screen, ◦ measures of hepatic and renal function. The cause of the status should be identified urgently and may require treatment in its own right.

41. Management: First line medication: BZPs. Second line medication: Phenobarb > phenytoin (in patients under the age of 1-2 yrs.)

42. Management: Other investigations and management strategies include: Stat ABG/VBG (with lytes, Hb, & lactate). Full set of labwork including LFT’s, ammonia, urine and blood cultures. Empiric antibiotics (if needed). Head U/S or CT

43. Management of Hyponatremia

44. Acute Hyponatremic Hypovolemia with Neurologic Symptoms Treatment of choice is 3% hypertonic saline at 100 ml/h. ◦ For each 100 ml of 3% hypertonic saline, serum sodium concentration increase s by approximately 2 mmol/l. ◦ Duration of hypertonic saline treatment is based on the improvement in the patient’s symptoms and signs. Patients with acute hyponatremia ◦ may be lethargic, disoriented, agitated, and have anorexia and nausea. ◦ Physical findings: abnormal sensorium, pathological reflexes, Cheyne- Stokes respiration, hypothermia, and seizures. Severe symptoms: seizures, obtundation, and coma, ◦ 3% sodium may be infused at 4–6 ml/kg/h.

45. Acute Hyponatremic Hypovolemia with Neurologic Symptoms The immediate treatment of hyponatremic seizures in neonates: ◦ provide enough sodium in a 10-minute period to elevate serum sodium level to 125 mEq/L by using 3% normal saline solution. The amount of sodium required : (125 -?) x (0.6) x (wt kg) = X mEq ?= patient’s serum sodium, 0.6 is the dilution constant, X = number of mEq to correct sodium level to 125 mEq.

46. Treatment of CAH Patients suspected of 21-hydroxylase deficiency should have the following bloodwork sent: 1.Electrolytes 2.Glucose 3.17-hydroxyprogesterone levels 4.Cortisol levels 5.Aldosterone and renin levels.

47. After drawing appropriate bloodwork: 1.Patients with dehydration, hyponatremia, or hyperkalemia should receive a bolus of isotonic crystalloid to restore volume. 2.Hypoglycemic patients should receive a dextrose bolus infusion. 3.Patients suspected of adrenal insufficiency should be treated with steroids empirically (i.e. rather than waiting for the results of confirmatory studies). Treatment of CAH

48. When administering steroids: ◦ Use an initial dose of HC 1-2 mg/kg IV (followed by q6h dosing)  The disadvantage of hydrocortisone is that it will confound any ACTH-Stim testing.  The advantage of hydrocortisone is that it is a complete steroid—with both glucocorticoid and mineralocorticoid activity.

49. Glucocorticoids: hydrocortisone is the glucocorticoid of choice during childhood. ◦ Longer-acting glucocorticoids, such as prednisolone and dexamethasone, can be used in adults, but they are generally avoided in children because of concerns about growth suppression. ◦ Hydrocortisone is recommended in the pediatric population because of its lower potency, which permits easier titration of appropriate doses. Mineralocorticoids: to control electrolytes and plasma renin activity. ◦ Mineralocorticoid replacement is achieved with fludrocortisone. Treatment of CAH

50. Infants with salt-losing CAH often need sodium chloride supplementation. ◦ Routine salt supplementation is not usually needed after the first 6-12 months of life. ◦ Additional salt intake may be needed with exposure to hot weather or with intense exercise. Treatment during physical stress, e.g. febrile illness, surgery, trauma: ◦ Patients with classic CAH need increased, e.g. doubling or tripling, doses of hydrocortisone. ◦ Intravenous hydration may be required. ◦ Hypoglycaemia may occur with exercise, illness or fasting. Intake of carbohydrates and glucose should be increased. Treatment of CAH

51. All patients should wear or carry medical alert identification specifying adrenal insufficiency.

52. Etiopathogenesis

53. Speiser, et al. New England Journal of Medicine, 2003

54. Adrenal CrisisPrimary Congenital Adrenal Hypoplasia/Aplasia Congenital Adrenal Hyperplasia Adrenal Hemorrhage Adrenocorticotrophic Hormone unresponsiveness Acute IllnessAdrenoleukodystrophySecondary Differential Diagnosis

55. Congenital Adrenal Hypoplasia Acutely in the neonatal period Primarily affects boys Mutation of DAX1 Hypogonadotropichypogonadism = cryptorchidism

56. Adrenocorticotrophic Hormone Unresponsiveness No salt losing manifestations Hypoglycemia, seizures and hyperpigmentation in first decade of life Marked adrenocortical atrophy with relative sparing of the zonaglomerulosa Both sexes equally affected, autosomal recessive Mutation in the gene for ACTH receptor

57. Adrenal Hemorrhage Neonatal period due to difficult labor Presenting signs: abdominal mass, anemia, unexplained jaundice or scrotal hematoma May be due to an infection (ex. Tuberculosis, meningococcemia)

58. Adrenoleukodystrophy Adrenocortical deficiency is associated with demyelination in the CNS Impaired β -oxidation in peroxisomes =  levels of very long chain fatty acids found in tissues and body fluids Rare autosomal recessive disorder in neonates

59. Reserved slides

60. Types of Status Epilepticus Generalized Status ◦ Convulsive: generalized convulsive tonic-clonic status epilepticus (SE) is the most frequent type ◦ Absence ◦ Secondarily generalized: accounts for ~75% of generalized SE ◦ Myoclonic ◦ Atonic (drop attack): especially in Lennox-Gastaut syndrome Partial Status (usually related to anatomic abnormality) ◦ Simple (Epilepsy Partialis continuans) ◦ Complex ◦ Secondarily generalized Handbook of Neurosurgery by Greenberg