STATUS.EPILEPTICUS.CHILDREN.pediatrics. SE

Status epilepticus in children ppt

1. PEDIATRIC STATUS EPILEPTICUS Dr. SARFARAZ AHMAD Assistant Professor Pediatrics MMIMSR

2. Definition of Status Epilepticus In children, unprovoked, afebrile seizures typically last <4 minutes, and seizures that last >5 minutes are unlikely to remit spontaneously. SE that lasts >30 minutes is less likely to respond to anticonvulsants and likely to cause neuronal injury. So An operational definition of SE is seizure activity lasting >5 minutes. Status epilepticus (SE) is a medical emergency that should be anticipated in any patient who presents with an acute seizure. The ILAE has refined the definition of SE to reflect the time at which treatment should be initiated (t1 ) and time at which continuous seizure activity leads to long-term sequelae (t2 ) such as neuronal injury.

3. The classical definition of status epilepticus (SE) is seizure activity, either continuous or episodic, without complete recovery of consciousness, which lasts for at least 30 minutes. This definition was based based on animal studies that showed evidence of neuronal damage after this time point, but this has been reduced to emphasize the risks involved with the longer durations and the need for early and aggressive pharmacologic intervention.

4. Types and Time frames For generalized tonic-clonic seizures, SE is defined as continuous generalised convulsive activity or recurrent generalized convulsive seizure activity without regaining of consciousness (t1=5min, t2 ≥ 30 min). The definition differs for SE consisting of focal seizures with impaired awareness (t1 = 10 min, t2 = 30 min) and absence SE (t1 = 10-15 min, t2 = unknown).

5. Time after which if seizure don’t terminate , pt considered in SE (t1) Time after which ongoing seizure have long term consequences (t2) Convulsive SE 5 min 30 min Focal SE with impaired consciousness 10 min >60 min Absence SE 10-15 min unknown

6. Practically any patient who presents to health care facility in actively convulsing state should be assumed to be in SE and treated.

7. Epidemiology & Outcomes Incidence: Ranges between 10 and 60 per 100,000 population. Highest in children <5 years: ~100 per 100,000 children. Clinical Context:~30% of SE cases are a patient’s first seizure.~40% of these patients later develop epilepsy. Mortality rate: 4–5%, primarily due to underlying etiology. New neurologic deficits: ~14% risk, 12.5% due to underlying pathology.

8. Types of SE based on Semiology Febrile Status Epilepticus:- is the most common type of SE in children. Convulsive SE :- MC type of SE. -manifests as generalized tonic, clonic, or tonic-clonic.Seizures often begin focally but spread to involve the entire brain. Non convulsive SE :- can manifest as a confusional state, dementia, fluctuating mental status, hallucinations, paranoia, aggressiveness, catatonia, and/or psychotic symptoms. It should be considered in all children who present to the hospital in an encephalopathic state or in the intensive care unit when a child’s mental status fails to improve.

9. Neonatal SE: Neonates are unlikely to demonstrate GCSE or continuous seizures. Frequent, serial seizures without recovery of consciousness can occur. Neonatal seizures are frequently polymorphic and may involve rapid extensor or flexor posturing, tremor of extended extremities, apnea, eye deviation, or automatisms. Myoclonic SE: Myoclonic SE is characterized by irregular, asynchronous, small-amplitude, repetitive shock like myoclonic jerking of the face or limbs(<50msec ). Epilepsia partialis continua: Focal motor clonic and/or myoclonic seizures that persist for days, months, or even longer are caused by tumor, vascular etiologies, mitochondrial disease (MELAS), and Rasmussen encephalitis.

10. Terminology Refractory SE :- is SE that has failed to respond to therapy, with at least two medications (such as a benzodiazepine and another 2 nd line medications such as phenytoin, levetiracetam, valproic acid). Superrefractory SE :- is SE that has failed to resolve, or recurs, within 24 hr or more despite therapy that includes a continuous infusion such as midazolam and/or pentobarbital.

11. New-onset refractory status epilepticus (NORSE) has been identified as a distinct entity that can be caused by almost any of the causes of SE in a patient without prior epilepsy. SE without clear etiology after initial investigations (brain imaging, blood, CSF) ruling out stroke, infection, toxic/metabolic causes. Often in previously healthy children, no prior seizures. May follow prodromal flu-like illness. It also is often of unknown etiology, presumed to be encephalitic or postencephalitic (inflammatory/autoimmune , rare infections, genetic causes) can last several weeks or longer, and often, has a poor prognosis( 10% mortality, upto 66% long-term disability .

12. Devastating epileptic encephalopathy in school-age children (DESC) ,Febrile Infection-Related Epilepsy Syndrome (FIRES) in Children ( FIRES) :- NORSE subtype(>2yr age ) with preceding febrile illness 1–14 days before seizure onset.Fever not required at seizure onset. often responsive to the ketogenic diet.

13. Etiology Neurological Causes New-onset epilepsy (any type). Acute head trauma. Ischemic stroke (arterial/venous). Intracranial hemorrhage. Brain tumors. Brain malformations, neurodegenerative disorders, progressive myoclonic epilepsy, storage diseases. Infectious/Inflammatory Causes Encephalitis (e.g., herpes simplex, Bartonella, Epstein-Barr virus, Mycoplasma,HHV-6). Meningitis. Autoimmune encephalitis (e.g., anti-NMDA receptor, SREAT, anti-voltage-gated potassium channel syndromes). Postinfectious encephalitis, acute disseminated encephalomyelitis (ADEM).

14. Metabolic ,toxic and Genetic Causes Hypoglycemia, hypocalcemia, hyponatremia, hypomagnesemia. Inborn errors of metabolism (e.g., nonketotic hyperglycinemia, MELAS). Folinic acid, pyridoxine, pyridoxal-phosphate dependency. Ion channel-related epilepsies (sodium/potassium channel mutations). Drug intoxication (e.g., tricyclic antidepressants in children),Drug/alcohol misuse (adolescents).Drug withdrawal/overdose in patients taking AEDs. Systemic Conditions Hypoxic-ischemic injury (e.g., after cardiac arrest). Hypertensive encephalopathy. Posterior reversible encephalopathy syndrome (PRES). Renal or hepatic encephalopathy.

15. PATHOPHYSIOLOGY Failure of AMPA Glutamate Receptor Desensitization: Persistent increased neuronal excitability. Sustains seizure activity. Reduction of GABA-Mediated Inhibition: Intracellular internalization of GABA receptors. Decreases inhibitory control, prolonging seizures. Clinical Implications: SE less likely to stop with prolonged duration.Benzodiazepines less effective over time due to reduced GABA receptor availability. AMPA( alpha amino 3-hydroxy 5-methyl lisoxazole 4-proproinate )

16. Sustained Seizure Activity Causes CNS damage MECHANISM:- uncontrolled neuronal firing -> excess glutamate action->sustained high influx of calcium ions into neurons leads to cell death-> mitochondrial dysfunction and oxidativestressq(“excitotoxicity”). GABA is released to counteract this, but GABA receptors eventually desensitize Systemic factors like hyperthermia, hypoxia, or hypotension exacerbate the injury. Increased cerebral metabolic rate during SE->Compensatory increase in cerebral blood flow.After ~30 minutes, blood flow fails to match metabolic rate-> inadequate cerebral oxygen tensions-> neuronal injury.

17. Clinical presentation MC is convusing SE. During initial compensatory phase-sympathetic overdrive leading to- - increased C.O -increased BP -increased RBS -increased blood lactate levels

18. Decompensation –homeostatic failure Reduced 🡪C.O/ BS/SPO2 levels leading to 1. Cardiorespiratory collapse 2. Electrolyte imbalance 3. Rhabdomyolysis - Renal tubular necrosis 4.Hyperthermia 5 . Raised ICP & cerebral edema

19. Clinical Evaluation It is important to obtain a brief history including any history of seizure disorder, other symptoms (fever), medication usage and allergies to medications. This can be completed by a designated person not immediately involved in the acute resuscitation. This history will allow a simultaneous search for cause and focused physical examination to be completed while termination of the seizure is undertaken.

20. MANAGEMENT Admit all SE patients to ICU. Broadly divided into :- 1)Initial stabilization 2)Seizure termination 3)Evaluation and Treatment of underlying cause Both diagnostic evaluation and seizure control should be achieved simultaneously to improve the outcome.

21. Initial Stabilization: Airway: airway patency is maintained, 100 % O 2 should be provided to prevent hypoxia Breathing: in case of respiratory failure if GCS score is less than 8, rapid sequence intubation must be done. Circulation: IV access should be secured promptly. In case IV access is not easily accessible buccal, rectal or intraosseus route can be considered Vital parameters like Heart rate ,Respiratory rate,temperature, continuous EEG, and Oxygenation saturation should be monitored

22. Initial Management of Status Epilepticus in Children Immediate attention to airway, breathing, circulation (ABC). Continuous monitoring of vital signs, including ECG. Identify and Manage Etiology: e.g., hypoglycemia Labs: Glucose, sodium, calcium, magnesium, CBC, metabolic panel. Additional tests: Blood/spinal fluid cultures, toxic drug screens, inborn errors of metabolism, AED levels. Imaging: CT scan. Continuous EEG to: 1.Rule out pseudo-SE/other movement disorders (chorea, tics, rigors, clonus, posturing). 2.Identify SE type (generalized vs. focal). 3.Monitor subtle seizures/electroclinical dissociation.

23. Seizure termination Pharmacotherapy:- Mechanisms of action of AEDs, mainly involving modulation of voltage-activated ion channels, potentiation of GABA, and inhibition of glutamate. 1 . Start for convulsive seizures lasting >5 minutes.👇 🔸️First-Line Agents (Benzodiazepines) : IV lorazepam (preferred) / IV diazepam; IM midazolam if no IV access. Alternatives: Buccal/intranasal midazolam, intranasal lorazepam, rectal diazepam. 2. If seizures persist 5 min after first dose, give second dose (@10 min). Monitor for respiratory depression. 3. If Seizures persist 5 min after second benzodiazepine dose (till 15 min), give one of the following: 🔸️️second line agents : Fosphenytoin: 20 mg/kg loading dose; check levels after 2 hours; maintenance dose after 6 hours if needed. Valproate: 40 mg/kg loading dose; avoid in <2 years, hepatic dysfunction, mitochondrial disease. Levetiracetam: 60 mg/kg loading dose; well-tolerated.

24. Refractory SE : Continuous Infusion Seizures persist after benzodiazepine plus secondline therapy.👇 Start IV bolus + continuous infusion (Intubation often required) : Midazolam, propofol, pentobarbital, thiopental. Adjust based on clinical/EEG responses. Monitoring: EEG essential (especially in intubated/paralyzed patients) to stop electrographic seizures. Goal: Burst suppression (EEG flattening, 8–20 sec intervals). Recommendation: Definitive control within 60 min (Neurocritical Care Society Guidelines).

25. Super-refractory Status Epilepticus: Treatment Strategies Seizures persist/recur despite 24 hours of general anesthesia (midazolam, pentobarbital, propofol).👇 Continuous infusions (midazolam, pentobarbital, propofol). Polytherapy: Fosphenytoin, valproate, phenobarbital, levetiracetam, topiramate, lacosamide. Ketamine infusion (NMDA antagonist, effective for NMDA upregulation). Ketogenic diet (response in ~1 week; challenging with pentobarbital).

26. Immunotherapy and Advanced Therapies for Superrefractory SE Immunotherapy: Used in SRSE of unclear etiology (e.g., anti-NMDA receptor encephalitis, CNS vasculitis) Options: IV steroids, immunoglobulins, plasma exchange. Initiated empirically if autoimmune etiology suspected. Advanced Therapies: Inhaled anesthetics (isoflurane): Limited by adverse reactions, anesthesiologist needed. Induced hypothermia: Safety/efficacy under investigation. Neurosurgical options: Hemispherectomy (Rasmussen encephalitis), focal resection (cortical dysplasia). Emerging: Allopregnanolone (neurosteroid, in trials). Others: VNS, ECT, transcranial magnetic stimulation (epilepsia partialis continua).

27. 6.Pyridoxine:- Pyridoxine-dependent seizures occur due to a rare AR mutation in the ALDHTA1 gene which encodes antiquitin. This condition usually presents in the early infantile period with seizures that are refractory to standard anticonvulsants. Intravenous pyridoxine 100mg trial should be considered in children< 2 age with refractory SE.

28. TAKE HOME MESSAGES: Status Epilepticus is a life threatening medical emergency that requires prompt recognition and management. Attention to airway,breathing and circulation simultaneously while treating seizure. Early Rx aborts SE faster and prevents neuronal damage. Initial management should consist of parenteral benzodiazepines ; any agent by any route may be used depending upon the availability and urgency. Aggressive therapy is required for management of SE as prolonged seizures are less responsive to therapy.