Super-Refractory Status Epilepticus: A Therapeutic Challenge in Paediatrics

Abstract

CaSe 1A seven-year-old boy with fever and persisting seizures (generalized tonic-clonic seizures) on multiple anti-epileptic medications {phenytoin (6 mg/kg/day), phenobarbitone (6 mg/kg/day) and valproate (20 mg/kg/day)} was referred to our hospital. At admission, he was in generalized convulsive status epilepticus. Blood investi gations were normal. The dosage of antiepileptic medications was optimized. Cerebrospinal Fluid (CSF) analysis was suggestive of viral meningoencephalitis (lymphocytic leukocytosis, mildly elevated protein, normal glucose with sterile culture) however, specific cultivable viral titers in CSF (Japanese Encephalitis, Herpes Simplex Virus, Dengue, Enterovirus) were negative. Magnetic Resonance Imaging (MRI) brain with contrast showed increased meningeal enhancement and Electroencephalogram (EEG) showed generalized epileptiform activity. He persisted in having seizures on second line Anti-Epileptics Drugs (AEDs) {valproate 40 mg/ kg/day, levetiracetam 60 mg/kg/day} and hence was started on midazolam infusion and mechanically ventilated. Thiopental was added on, following which he remained seizure free for 120 hours with EEG showing burst suppression. Thiopental was gradually tapered and stopped however he had a recurrence of seizures. He was continued on intravenous midazolam, AEDs (Phenytoin 6 mg/kg/day, phenobarbitone 6 mg/kg/day, valproate, levetiracetam, clobazam (10 mg/day) and zonisamide 400 mg/day). He required tracheostomy for prolonged ventilation and had other comorbidities like ventilator-associated pneumonia which were managed accordingly. CSF analysis for Anti-NMDAR and voltage-gated potassium channels were negative. He gradually improved, and seizures subsided with normal EEG.At follow up he had persistent residual neurological deficits (cognition deficits and spasticity) with occasional breakthrough seizures (generalized tonic-clonic seizures). AEDs were gradually tapered and continued on levetiracetam and clobazam. He was under regular follow up for 40 months. CaSe 2A seven-year-old girl with a history of fever and persisting seizures (generalized tonic-clonic seizures) was admitted. We hereby reported three cases of super refractory seizures as they posed a therapeutic challenge. All three children were aged 6-7 years with prior normal developmental history and no medical illness. Viral meningoencephalitis, fever induced refractory status epilepticus, and auto-immune encephalitis was the probable aetiology in the cases studied. Midazolam, pentobarbital, and ketamine are the most commonly used anaesthetic agents. Phenytoin, phenobarbitone, valproate and levetiracetam are the most commonly used antiepileptic agents. All three cases had residual neurological deficits and morbidities like pneumonia and sepsis. SRSE is associated with high rates of mortality and morbidity necessitating immediate treatment.and CSF analysis including viral titers were normal. MRI brain with contrast showed subtle enhancement along the sulci. EEG showed slow waves with suppressed background [Table...

Treatment of Refractory Convulsive Status Epilepticus: A Comprehensive Review by the American Epilepsy Society Treatments Committee

“…159 Nene et al conducted a class II study of 118 patients older than age 60 years with established CSE who received 20 to 25 mg/kg of either LEV or VPA, and there was no difference in efficacy. 44 In a class II study of 73 adults, PB 20 mg/kg was superior to VPA 30 mg/kg in initial efficacy as well as in a lower recurrence rate of seizures within 24 hours ( P <.05). 160 …”

“…Refractory status epilepticus was controlled after 30 minutes in 80% of VPA and 85% of diazepam infusion patients (P ¼ NS). 158 44 In a class II study of 73 adults, PB 20 mg/kg was superior to VPA 30 mg/kg in initial efficacy as well as in a lower recurrence rate of seizures within 24 hours (P <.05). 160 In a class III study of 30 children and adults (aged 14-73 years) randomized to VPA or PHT both at 20 mg/kg, established CSE cessation was 73.3% and 60%, respectively (P ¼ NS).…”

“…While some case reports did not find a response, [44][45][46][47] and while some larger series are not sufficiently granular to determine specific KET treatment outcome in RSE, 48 others report a response in most of the episodes, [49][50][51] or partial response in their series. [52][53][54][55] In a large multicenter class IV study of 58 children and adults (which included NCSE cases), KET was started after a median of 9 days, yet it controlled RSE "likely" in 12% and "possibly" in additional 20%.…”

Pediatric refractory and super-refractory status epilepticus

“…Within the acute symptomatic etiology, CNS infections (e.g. herpes simplex virus (HSV), HIV, neurocysticercosis, malaria, tuberculosis), viral/autoimmune encephalitis and meningitis are common causes [7,[24][25][26][27][28][29][30].…”

Therapeutic hypothermia for pediatric refractory status epilepticus May Ameliorate post-status epilepticus epilepsy

“…Refractory status epilepticus is defined as clinical or electroencephalographic seizures lasting >60 min despite treated with at least one first-line AED (e.g., benzodiazepine) and one second-line AEDs (e.g., phenytoin, phenobarbital, or valproate) [ 2 , 5 , 6 ]. Super-refractory status epilepticus (SRSE) is defined as SE that has persisted or recurred for ≥24 h after the onset of general anesthesia treatment [ 7 ]. Both RSE and SRSE are considered neurologic emergencies, because the patient can develop complications including hypoglycemia, brain injury, rhabdomyolysis, related kidney injury, prolonged intensive care unit (ICU), hospital stays, and even death [ 4 , 8 ].…”