ACUTE MANAGEMENT OF SEIZURES IN CHILDREN.pptx

Describes briefly what seizures are, their types, how to manage them with videos on some seizure types.

1. ACUTE MANAGEMENT OF SEIZURES IN CHILDREN Dr Joel Boakye HO TEMA GENERAL HOSPITAL

2. Outline Definitions Stages of a seizure Aetiology Pathophysiology Signs and symptoms Investigations Management Epilepsy syndromes Complications Seizure Mimics Prognosis

3. Definition A seizure is defined as an excessive and/or hyper synchronous activity of cortical neurons that results in transient neurological symptoms

4. Acute seizure definition The International League against Epilepsy (ILAE) defines acute symptomatic seizures as seizures occurring in close temporal association with an acute systemic, metabolic, or toxic encephalopathy or in association with an acute central nervous system disorder ( Eg:infection )

5. SOME TERMS USED TO DESCRIBE SEIZURES Reflex seizure: a seizure constantly evoked by a particular stimulus (trigger) that lowers seizure threshold (e.g., flashing lights; see “Seizure triggers”) Unprovoked seizure: a seizure that occurs in the absence of an identifiable cause or beyond the specified interval after an acute CNS condition Ictal: symptoms & signs occurring during a seizure Interictal : symptoms & signs occurring between the seizures
Postictal: symptoms and signs occurring signs after a seizure

6. SOME TERMS USED TO DESCRIBE SEIZURES CONTINUED… Focal seizure ( partial seizure) : The World Health Organization (WHO) defines focal seizures as seizures that affect initially only one hemisphere of the brain. These seizures are generated in and affect just one part of the brain – a whole hemisphere or part of a lobe. Generalised seizure: occurs when the abnormal electrical activity causing a seizure begins in both halves (hemispheres) of the brain at the same time.

7. STAGES OF A SEIZURE

8. STAGES OF A SEIZURE

9. AETIOLOGY Metabolic disorders: Hypoglycemia , Hyper glycemia . Symptoms of hypoglycemia In new borns Include: Jitteriness, apnea, unconsciousness, Poor feeding, cyanosis, lethargy, hypothermia NB: Jitteriness is diff from a seizure and is suppressed by flexing the limb

10. AETIOLOGY Uremia,acute porphyrias , Hypercreatinemia

11. AETIOLOGY Acute CNS infections ( Meningitis,Malaria , neurocysticercosis , encephalitis, toxoplasmosis, . Rubella, cytomegalovirus infection, Herpes simplex. Syphillis )
Traumatic brain injury Structural lesions: Brain tumors, Hippocampal sclerosis, Congenital cerebral or Arteriovenous malformation, microcephaly, Megalocephaly ,cortical dysgenesis

12. AETIOLOGY MRI OF A BRAIN WITH HIPPOCAMPAL SCLEROSIS CAUSES: VERBAL MEMORY IMPAIRMENT & DRUG RESISTANT EPILEPSY MRI SHOWS : REDUCED HIPPOCAMPAL VOLUME , Increased Signal intensity on T2 weighted image and disturbed internal architecture

13. AETIOLOGY CONTINUED Prescription drug toxicity eg : isoniazid overdose- causes decrease in GABA availability, aminophylline toxicity, insulin overdose Exacerbations of autoimmune disorders (e.g., SLE), Rasmussen encephalitis, automimmune encephalitides Severe dehydration: Due to electrolyte imbalances. ( Eg : Na+ , K+) . Affects action potential generation

14. AETIOLOGY GENETICS Genetic mutations affecting ion channels or transmitter receptors (e.g., mutations in KCNQ2- potassium channel subfamily Q 2 or SCN1A genes)
Chromosomal abnormalities (e.g., Angelman syndrome, Prader -Willi syndrome, Rett syndrome)
Genetic metabolic disorders (e.g., PKU, congenital disorders of glycosylation, lysosomal storage diseases, peroxisomal biogenesis disorders)

15. MELAS:Mitochondrial diseases (e.g., MELAS)- mitochondrial encephalomyopathy , lactic acidosis- rare genetic condition in childhood

16. AETIOLOGY ANGELMAN SYNDROME

17. AETIOLOGY PRADER WILLI SYNDROME

18. Aetiology continued Electrolyte imbalances- hypocalcemia , hyperkalemia, Hypomagnesia , hyponatremia, hypernatremia Recreational drug use . Tuberculosis- tuberculous meningitis, tuberculoma Oxygen deprivation ( anaemia ) Stress – emotional/physical- extreme – in epileptics

19. AETIOLOGY HEAD CT SCAN WITH TUBERCULOUMA Characteristic CT finding is a nodular enhancing lesion with a central hypodense region

20. Aetiology continued… TRIGGERS Fever - Increases Glutamergic excitation, inhibits GABA Flashing lights ( eg strobe lights- at some frequencies: eye> thalamus>> cortical neurons, video games) NB: 16 th DECEMBER 1997, “the electric soldier porygon ” Episode of Pokemon caused about 600 children across Japan to have seizure attacks. This caused that episode to be banned. The episode contained repetitive visual effects that induced photosensitive epileptic seizures

21. AETIOLOGY Music ( musicogenic seizures) – specific frequencies or pitch of music can trigger musicogenic seizures in individuals with epilepsy who have a low threshold or tolerance for these sounds.

22. AETIOLOGY CONTINUED… TRIGGER S Sleep deprivation – in people with epilepsy.
Hormonal changes ( eg : catamanial epilepsy) - a pattern of seizures that changes in severity during specific phases of the menstrual cycle Poor adherence to anti epileptic drugs
Excessive physical exertion in people with epilepsy

23. PATHOPHYSIOLOGY Action Potential Generation Neurotransmitter release Seizure Initiation (poor inhibition/excessive excitation)

24. Pathophysiology Neurons generate action potentials in order to transmit impulses.

25. PATHOPHYSIOLOGY ACTION POTENTIAL GENERATION Stimulation>> DEPOLARISATION(Na+ influx) >>INCREASED MEMBRANE POTENTIAL>> RE POLARISATION (K+ efflux) >>> HYPER POLARISATION ( K+ further efflux due to slow k+channel closure)

26. PATHOPHYSIOLOGY CONTINUED NEUROTRANSMITTER RELEASE Calcium ion influx activates docking proteins on neurotransmitter vesicles allowing vesicle to fuse with pre synaptic membrane and release neurotransmitter to post synaptic membrane receptor as action potential propagates towards dendrites

27. PATHOPHYSIOLOGY CONTINUED Depolarization of the neuronal membrane that travels down the axon to release neurotransmitters at the terminal causes ACTION POTENTIAL
Endogenous substances called neurotransmitters are responsible for sending signals across a synapse from a neuron to a target cell.

28. PATHOPHYSIOLOGY CONTINUED… Depending on the characteristics of the receptors, neurotransmitters can either be excitatory or inhibitory. The primary excitatory neurotransmitter in the brain and spinal cord is glutamate.

29. PATHOPHYSIOLOGY CONTINUED The primary excitatory neurotransmitter in the brain and spinal cord is glutamate. GABA is the primary inhibitory neurotransmitter. GABA is the primary inhibitory neurotransmitter.

30. PATHOPHYSIOLOGY CONTINUED… GLUTAMATE PATHWAY (EXCITATORY) Binds to NMDA / AMPA receptor on POST SYNAPTIC neuron >>> Influx of cations(Na+, ca2+, Mg2+) >>>> De polarisation>>> ACTION POTENTIAL! - IN A SEIZURE; More glutamate release>>> more cation influx>>> more action potential bursts>> excessive synchronous firing of neurotransmitter.

31. PATHOPHYSIOLOGY CONTINUED GABA PATHWAY (INHIBITORY) GABA R Receptors are defective >>> no influx of anions to cause repolarisation and hyper polarisation>>>> No inhibition of action potentials>>>> excessive synchronous firing

32. PATHOPHYSIOLOGY CONTINUED… SEIZURE INITIATION: Characterised by 2 concurrent events
- high frequency bursts of action potentials, influx of extracellular calcium >> Opening of voltage dependent Na+ channels>> influx of na + >>prolonged depolarization>>Generation of repetitive Action potentials

33. PATHOPHYSIOLOGY CONTINUED Sufficient burst activity >> recruitment of surrounding neurons>>loss of surround inhibition>> spread of seizure activity into contiguous areas via local cortical connections>>spread to more distant areas via long association pathways eg corpus callosum.

34. Clinical features Lip smacking Rapid Blinking Tapping Exploratory movements with hands Staring Loss of consciousness Drooling or frothing from mouth Headache Fatigue or sleepiness

35. CLINICAL FEATURES CONT… . Pedalling abnormal eye movements – eye deviation Yawning Apnea Jerking movements of arms and legs

36. Seizure video Clonic movement of right arm and leg in a conscious child Right mouth Jerk with contraction of right arm in a child Partial seizure

37. GENERALISED SEIZURE Unconscious child with rhythmic jerking of whole body

38. MANAGEMENT Simple febrile seizures do not require treatment if brief . Treatment includes measures to reduce temperature and to find and treat the underlying cause. Prolonged and repeated seizures need investigation and treatment.

39. Management outline Stabilisation phase Initial therapy phase Established convulsive status

40. Management Mainstay is to abort the seizure as soon as possible. The longer seizure lasts, the more difficult it is to abort. Diagnostics and management should occur concurrently

41. ACUTE MANAGEMENT CHECKLIST

42. ACUTE MANAGEMENT CHECKLIST Take a history Do a physical examination to ascertain possible cause ( eg Neuro infection, Established epilepsy, head trauma) . Look out for : Dysmorphisms , neurocutaneous manifestations Examine cranial nerves, motor exams, Neuro exams

43. ACUTE MANAGEMENT CHECKLIST Establish that incident is a SEIZURE
Most seizures last <5minutes
Seizures >30minutes are STATUS EPILEPTICUS/ When two or more seizures occur sequentially without return to consciousness between seizures. A seizure that lasts longer than 5 minutes, or having more than 1 seizure within a 5 minutes period, without returning to a normal level of consciousness between episodes is called status epilepticus. This is a medical emergency that may lead to permanent brain damage or deathdeath ( Johnhopkins.org , 2023)

44. MANAGEMENT – TIMELINE FIRST AID, ABC, GLUCOSE 5 MIN 1 st BENZODIAZIPINE. 10 MIN 2 ND BENZODIAZIPINE 10MIN 2nd LINE DRUG 20MIN 3 rd LINE DRUG AVOID DELAYS IN STEPS, But Don’t also be in a hurry

45. General measures – stabilisation phase (Check list) Children who come in with an active convulsion should be stabilised -ABC assessed – to ensure child has nothing in mouth, is ventilating and pulse is stable for age.
-Child should be turned on side in case of excess oral secretion
- remove any clothing over face , to facilitate respiration and prevent injuries
- MEASURE VITALS including RBS (Random blood sugar)

46. Stabilisation phase continued… Put on OXYGEN EVEN IF SPO2 IS >95% .Because; acute seizures place a high metabolic demand on the brain and cardiovascular system. -If blood oxygen is low, suction may be needed -

47. Stabilisation PHASE CONTINUED.. Do not put anything in the mouth to prevent oral injuries
-Note that the efficacy of oxygen administration is reduced, whiles giving oxygen in a tonic clonic seizure so aborting the seizure, while suctioning is very important
- Pass IV line and take samples for diagnostic assessment.

48. Stabilisation phase continued… INVESTIGATIONS
NB- Treatment to halt seizures should proceed as diagnostics are being done
-Do Thick and thin film for malaria parasites and RDT for malaria

49. STABILISATION PHASE Febrile seizure- check temperature- high axillary temperature >38 degrees Celsius
IF You suspect Acute infection including meningitis – FBC; looking for elevated WBC. Consider LP for CNS infection

50. STABILISATION PHASE If you suspect Renal failure, hypertensive crises- Creatinine, BUE, BP with vitals
If you suspect it’s due to an electrolyte abnormality, check the electrolytes and address it ( eg : free water restriction in hyponatremia)

51. STABILISATION PHASE CONTINUED HYPOCALCEMIA : IONISED CALCIUM <0. 75mmol/l Full term Ca <1.9mmol/l Preterm Ca <1.75mmol/l SYMPTOMS: Irritability, jitteriness, cyanosis, seizures, brisk reflexes , stupor Treat with 1-2ml/kg of 10% calcium gluconate (100-200mg/kg) by slow IV infusion over 10min If patient can feed, give orally with feeds( in divided doses )

52. Stabilisation phase continued… If you suspect it’s due to a toxin or poisoning, toxicology screen . Some medications that can induce seizures are efavirenz , high dose penicillin and isoniazid NB: Betalactam antibiotics reduce threshold for seizure by binding to GABA receptors. This interferes with inhibitory Neuro transmission in the brain, reducing seizure threshold.

53. STABILISATION PHASE CONTINUED… If you suspect it’s due to anti epileptic drugs, assess dose. If too low, give standard dose , if dosage is therapeutic or toxic, avoid further dosing
If it’s due to trauma do a CT or MRI looking for acute blood loss
Check HIV status in children whose status is not known

54. Stabilisation phase continued… . MANAGEMENT WITH IV LINE - If patient is hypoglycemic ( RBS <2.5mmol/l in a well nourished child and <3mmol/l in a malnourished child) , correct it to treat seizures due to low glucose and to prevent hippocampal injury that might result in memory impairment, behavioral problems and/ possibly long term epilepsy TREATING HYPOGLYCEMIA - Give 5ml/kg of 10% glucose solution rapidly by IV injection
-IF RBS remains low or hypoglycemia is still suspected, Give another bolus of 5ml/kg of 10% glucose after 30min.

55. STABILISATION PHASE CONTINUED FOR HYPOGLYCEMIA, OTHER LITERATURE RECOMMEND ; Early introduction of feeds if feasible Dextrose 10% @2cc/kg as IV Push followed by D10% Infusion at 60cc/kg/day Monitor blood sugar regularly aim at 3.5-5.0 mmol /l If patient remains hypoglycemic start glucagon 1mg/24hr as continuous infusion

56. Stabilisation phase continued… In healthcare facilities lacking the necessary equipment and expertise for intravenous administration of medications and fluids, nasogastric access for enteral treatments should be obtained. Unconscious children should be kept on maintenance IV fluids that include glucose or be given milk/sugar solution via nasogastric tube (NGT). TREATMENT WITHOUT IV LINE . - IF IV access can't be attained- give benzodiazipines via other routes , NB: treatment of hypoglycemia is best via IV routes

57. Initial therapy phase -If child is still convulsing, give benzodiazipines except in infants <2 weeks who should receive phenobarbitone instead --- because benzodiazipines linked to adverse effects in infants< 2 weeks. -Diazepam is most common benzodiazipine given at 0.25mg/kg IV , can also be given rectally in the pre hospital setting or a facility not equipped to administer IV @0.5mg/kg

58. Initial therapy phase continued… . If weight can't be known use table below {TABLE} - If child is stunted / wasted dose based on age of appearance instead of biological weight. - IF seizure stops spontaneously, treatment may be withheld NB- IM diazepam can be given but due to its erratic absorption, it's not recommended Higher doses of dzpm Can be given at facilities which have early ventilator and intubation support readily available. In their absence, significant caution in exceeding the dose is warranted.

59. Initial therapy phase continued… .. OTHER AGENTS THAT CAN BE GIVEN IN ACUTE SEIZURES 1. Paraldehyde - IM, RECTAL- less respiratory suppressive effects as compared to dIazepam 2. Midazolam - IV, IM, BUCCAL, INTRANASAL - 3. Lorazepam - IV, IM, INTRANASAL, BUCCAL - contraindicated in anyone on protease inhibitors, which substantially and unpredictably increase the half-life of this otherwise relatively short-acting sedative agent

60. Initial therapy phase continued… . IF seizure persists for more than 10minutes, after 1st dose of diazepam, give second dose . NB: More than 2 doses of benzodiazipine preceding the use of phenobarbitone is associated with an increased risk of respiratory failure and subsequent death where a ventilator is unavailable. - If second dose fails, give long lasting anti epileptic drug - AED should be in hand at first dose of BZDP.

61. RAISED ICP

62. DEXAMETHASONE PROTOCOL : If seizures are Recurrent and raised ICP is suspected .

63. Established status Epilepticus If child fails to respond to second dose of BZDP it’s status Epilepticus and warrants referral to tertiary facility

- Child requires close monitoring and evaluated for ventilatory and intubation support.
-long acting AED can be given prior to referral.
- If no IV access, pass intraosseous line.

64. Established status Epilepticus continued… - AEDS recommendations by WHO’S MhGAP , include; phenobarbitone , phenytoin and valproic acid.
Others where cost is not a problem- fosphenytoin , levetiracetam , and lacosamide .

65. Established status Epilepticus continued…

66. Established status Epilepticus continued…

67. Established status Epilepticus continued…

68. Established status Epilepticus continued… If parenteral aren't available, u can give enterals via NGT - enteral phenobarbital and valproate can be given. - If available oral levetiracetam can be given . Has good bioavailability after 1hr - If seizure continues after loading dose of parenteral AEDS, give another loading dose with a second Long acting AED for refectory status Epilepticus.eg of 15mg/kg phenobarbital was first given, give another 5mg/kg

69. Established status EPILEPTICUS continued SUPER REFRACTORY STATUS EPILEPTICUS Super-refractory status epilepticus is  a status epilepticus that continues for ≥24 hours despite anesthetic treatment, or recurs on an attempted wean of the anesthetic regimen

70. Super refractory seizure KETAMINE: Ketamine is a noncompetitive antagonist of glutamatergic  N -methyl- d -aspartate (NMDA) receptors. During prolonged seizures, the numbers and activities of GABA receptors gradually decrease; thus, the commonly used first-line and second-line antiepileptic drugs gradually fail. Simultaneously, the numbers and activities of glutamatergic NMDA receptors increase, often causing refractory status epilepticus (RSE) and thus providing the possibility of the use of ketamine to treat RSE. Example: DIAZEPAM is a positive allosteric modulator of the GABA receptor , hence; no GABA RECEPTOR, becomes futile PHENYTOIN is a GABA potentiator

71. Established status Epilepticus continued In addition to treatment listed in TABLE; IV ketamine can be given . In ventilated patients; -Give loading dose of IV ketamine @1.5mg/kg every 3 to 5 minutes until seizure on electroencephalogram stops. Maximum 4.5mg/kg. -Followed by maintenance infusion of 0.3-7.5mg/kg/hr.

72. Established status Epilepticus continued… In THE ABSENCE OF VENTILATION
- 1.5mg/kg IV load ff 15MCG/kg/min
NB- even brief cessation of infusion can let seizures recur
.Ideally, suppression of seizures with ketamine after refractory status epilepticus should be maintained for at least 24 h with at least one long-acting agent co-administered in therapeutic doses before discontinuation of ketamine, and if available, continuous EEG monitoring should be in
place to assure the seizures are controlled.
-Give single dose of a benzodiazepine in doses similar to those used for initial seizure management should be given just prior to discontinuing ketamine to avoid psychotic symptoms on wakening

73. MANAGEMENT FROM OTHER LITERATURE OTHER LITERATURE RECOMMEND : Propofol & Thiopentone as third line medications

74. OTHER LITERATURE RECOMMEND TREATMENT WITH THE FF PROTOCOL Rectal diazepam 5mg (1-3 years) , 10mg for 3 years and above or IV diazepam 0.2-0.5mg/kg/dose given slowly until convulsion stops If no response- paraldehyde 1ml/year of age to a maximum of 10ml rectally or by deep IM injection(1/2 into each buttocks) . Plastic syringes can be used but paraldehyde must be drawn up and used immediately.

If no response or use as step 2

75. PHENYTOIN
IV 15-20MG/KG Loading dose
Then 5mg/kg /day maintenance

PHENOBARBITONE
IV 10-15 mg/kg loading dose
Then 5mg/kg/day maintenance

4 midazolam
5. Magnesium sulphate 10-40mg/kg of 50% solution I’M STARTING DOSE

76. Others also recommend Phenobarbitone (1 st line drug) 10mg/kg IM repeat after 30mins Then commence maintenance 5mg/kg / day - Intramuscularly or orally Phenytoin- use if maximum phenobarbitone appears not to control seizures . Loading dose 10mg/kg Intramuscularly. Also repeat after 30minutes , then maintenance 5mg/kg/ day

77. EPILEPSY SYNDROMES West syndrome: Onset between 4-9 months Triad of : Infantile spasms, Epileptic spasms, Hypsarrhthmis on EEG, developmental regression Tx : Adrenocorticotropic hormone, Prednisone or vigabatrin

78. EPILEPSY SYNDROMES LENNOX GASTAUT SYNDROME Onset between 3-5 years Multiple seizures types; GTCS, Tonic seizures, absent seizures Worsening behavior Pharmacoresistant seizures Tx : sodium valproate,clobazam ,

79. complications of seizures EARLY: Physical trauma: such as: Tongue biting, posterior dislocation of the glenohumeral joint due to falling, polytrauma from a car accident CNS tissue damage due to hyperthermia C ardiorespiratory deficits E xcitatory toxicity

80. COMPLICATIONS OF SEIZURES IN CHILDREN EARLY: Hypoxia Hypercapnia Aspiration pneumonia Cerebral palsy

81. COMPLICATIONS OF SEIZURES LATE Cerebral palsy Neuronal damage Hypoxic ischemic encephalomyopathy intellectual disability

82. SEIZURE MIMICS conditions characterized by the presence of seizure-like activity occurring in the absence of EEG changes

83. Seizure MIMICS Benign Neonatal Sleep Mimics : Benign neonatal sleep myoclonus (BNSM) is a self-limiting disorder characterized by neonatal onset myoclonic jerks during non-rapid eye movement (NREM) sleep, and consistent cessation with arousal with absence of concomitant electroencephalographic findings Night mares / night terrors Sleep starts Staring episodes Day dreaming Infant gratification syndrome Breath holding spells

84. Seizure mimics Cataplexy : This sudden loss of muscle tone while a person is awake leads to weakness and a loss of voluntary muscle control despite being fully conscious. The consciousness helps differentiate it from a seizure. Funny movements Tics and mannerisms Dystonia

85. PROGNOSIS 3-9% Mortality within 30 days of status EPILEPTICUS Worse in low or middle income countries Neurological sequelae depends on the type of status epilepticus, duration, and age of child Duration: worse for prolonged Status epilepticus Age: worse neurological sequelae in infants (30% vs. 6% in older children) Seizure type: worse outcome for convulsive status epilepticus

86. References Ciccone , O., Mathews, M., & Birbeck , G.,( 2017, October ,28) , accessed November 12,2023.National library of Medicine. Management of acute seizures in children: A review with special consideration of care in resource-limited settings, accessed 12 November,2023 < https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246874/ >. Stanford medicine childrens health (2023) . Seizure and Epilepsy in children , accesses 12 November,2023.< https://www.stanfordchildrens.org/en/topic/default?id=seizures-and-epilepsy-in-children-90-P02621> Who (2023,February 9), accessed 02 December, 2023. Epilepsy . https://www.who.int/news-room/fact-sheets/detail/epilepsy#:~:text=Seizure%20episodes%20are%20a%20result,to%20severe%20and%20prolonged%20convulsions . Neequaye , J & Welbeck J. (2010) . Department of child health Korle bu teaching hospital. Convulsion (pp 9). Fathea , B. Seizure Disorders in children . Paediatric department UDS. AMBOSS GmbH (last updated 2023, November 09), accesses 11 November, 2023. Seizures and Epilepsy . Android Mobile app. Available from Https://amboss.com.

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