Authors :
Presenting Author: Daniel Biro, MD – University of Chicago
Daniel Biro, MD – Neurosurgery – University of Chicago; Katie Bullinger, MD, PhD – Assistant Professor of Neurology, Neurology, Emory University; Carlos Lara, MD – Fellow, Neurology, University of Chicago; James Tao, MD, PhD – Professor of Neurology, Neurology, University of Chicago; Naoum Issa, MD, PhD – Associate Professor of Neurology, Neurology, University of Chicago; Peter Warnke, MD Dr.med. – Professor of Neurosurgery, Neurosurgery, University of Chicago; Hiba Haider, MD – Associate Professor, Neurology, University of Chicago
Rationale:
New-Onset Refractory Status Epilepticus (NORSE) and Febrile Infection-Related Epilepsy Syndrome (FIRES) are rare forms of super refractory status epilepticus (SRSE). Previous reports described the use of neuromodulation to treat SRSE, including VNS, TMS, DBS (of the zona incerta, centromedian nucleus or anterior nucleus of the thalamus) and responsive neurostimulation of cortical onset seizures. We report a case of SRSE due to cryptogenic FIRES, treated with responsive neurostimulation (RNS) of the centromedian (CM) nucleus after Stereo-EEG monitoring.
Methods:
We report the case of a 26-year-old
man with cryptogenic FIRES, requiring sequential continuous infusions of midazolam, propofol & pentobarbital; these were weaned by HD 52 but seizures
persisted despite therapy with antiseizure medications (including cenobamate, clobazam, cannabidiol, lacosamide, levetiracetam, perampanel, and high dose phenobarbital)
, high dose steroids, plasmapheresis, IVIG, ketogenic diet, anakinra and electroconvulsive therapy.
His semiology consisted of right upper extremity and facial twitching, with frequent evolution to bilateral clonic or to bilateral tonic-clonic convulsions. 3T MRI was nonlesional and PET showed decreased uptake diffusely. Scalp EEG was non-localizing, with EMG artifact during motor seizures and abundant bi-occipital predominant 1-4 Hz generalized periodic discharges both during clinical seizures and interictally, suggesting potential involvement of deeper structures.
On HD
92, he underwent depth electrode placement in the bilateral pulvinar and centromedian nuclei. Clinical seizures demonstrated an ictal correlate of rhythmic sharp discharges recorded from the left centromedian contacts (Figure 1). Hypothesizing a left primary motor cortex onset with rapid spread to CM, an RNS system device was implanted in bilateral centromedian nuclei on HD 104.
Results:
After RNS System implantation, stimulation was started on postoperative day one at settings of 2.0 mA, 160 µS pulse width, 1.0 µC/Cm2 charge density, 5000msec duration, and 125 Hz frequency, and detection settings were adjusted to capture the electrographic seizures on ECoG. On day 4 after implant, seizures continued, so stimulation parameters were adjusted to 2.4 mA, 160 µS pulse width, 1.3 µC/Cm2 charge density, but with long bursts of 5000msec duration, and low frequency (5.9 Hz). This strategy was motivated by the observation of ~ 6 Hz repetitive spikes seen before seizure offsets, hypothesizing that stimulating at this frequency might accelerate seizure termination. After this change, histograms displaying counts of electrographic seizure activity continued to stabilize (Figure 2) and clinical seizures improved in frequency.
Conclusions:
This case demonstrates the feasibility and potential efficacy of responsive neurostimulation of the CM nucleus through diffuse neuromodulation of seizure networks to treat SRSE in cryptogenic NORSE/FIRES. Detection and stimulation settings will continue to be adjusted and long-term seizure outcome data will be presented.
Funding: None