Authors :
Presenting Author: Hiba Haider, MD – University of Chicago
Golbarg Saber, MD PhD – Resident, Neurology, University of Chicago; Carol Park, MD – University of Chicaog Medical Center; Matthew Smith, MD – University of Chicago Medical Center; Veronica Bonderski, PharmD, BCCCP – University of Chicago Medical Center; Sonam Thind, APN – University of Chicago Medical Center; Tareq Kass-Hout, MD – University of Chicago Medical Center; Shasha Wu, MD, PhD – University of Chicago Medical Center; Douglas Nordli, Jr, MD – University of Chicago Medical Center; Hiba Haider, MD, FACNS, FAES – Neurology – University of Chicago Medical Center
Rationale:
New-Onset Refractory Status Epilepticus (NORSE) and its subtype Febrile Infection-Related Epilepsy Syndrome (FIRES) are rare forms of refractory status epilepticus (RSE) in previously healthy individuals, with explosive onset of seizures that are refractory to antiseizure medication (ASM), continuous anesthetic infusions (CI), and often, immunomodulators. There have been recent reports of patients receiving intrathecal dexamethasone (IT-DEX) with improved RSE control. We report our experience with IT-DEX in two patients with FIRES.
Methods:
We present two patients (a twenty six year old adult man and nine year old boy) with FIRES who were administered IT-DEX during their hospitalization.
Patient 1 was a twenty six year old man presenting after rash and febrile illness followed four days later by convulsive seizures progressing to RSE. Prior to IT-DEX the patient had failed (at two different hospitals prior to transfer to our center) high dose steroid therapy, plasmapheresis, intravenous immunoglobulin (IVIG) and electroconvulsive therapy. IT-DEX therapy was initiated 48 days after seizure onset, while concomitant anakinra and ketogenic diet (KD) was continued. At the time of IT-DEX initiation, he was on seven ASMs and had been weaned off pentobarbital CI 5 days prior. After completion of IT-DEX, the patient was able to be further weaned off midazolam CI within 24 hrs.
Patient 2 is a nine year old previously healthy boy who presented with RSE after febrile illness. IT-DEX was initiated 60 days after onset. Prior to IT-DEX, he failed high dose steroid therapy & IVIG. At the time of IT-DEX initiation, in addition to ASMs he was on anakinra (later switched to tocilizumab), midazolam, ketamine, magnesium CI and KD.
Results:
For both patients, the IT-DEX dose was 0.25 mg/kg/dose for a total of six doses over two weeks. Both patients tolerated intrathecal delivery in the neuro-interventional suite without complications. Interval improvement in electrographic seizure burden was seen at day six for Patient 1; resolution of seizures was seen on day 16 for Patient 2 (Fig. 1). For Patient 1, IT-DEX treatment allowed for a successful wean of midazolam CI. Inflammatory markers (cytokine levels) in cerebrospinal fluid (CSF) and serum showed improvement pre- and post- IT-DEX for Patient 1 (Table 1), and are pending for Patient 2 at the time of submission.
Conclusions:
NORSE and FIRES carry high mortality and morbidity, and ensuing treatments for RSE confer additional risks. Expert consensus and various treatment strategies are increasingly available in the literature. Our experience with IT-DEX adds to the few existing reports of efficacy and tolerability with this emerging treatment. Our results suggest that the addition of IT-DEX may allow for successful weaning of CI, in addition to an improvement in seizure and ictal-interictal continuum burden, and proinflammatory cytokine profile. A caveat to our report is that IT-DEX was attempted late in the course of illness; earlier initiation of IT-DEX may have the potential to show additional benefit.
Funding: None