Low frequency centromedian thalamic nuclei deep brain stimulation for the treatment of super refractory status epilepticus: A case report and a review of the literature

•Centromedian thalamic DBS can be considered as a “rescue” treatment of sRSE.•High frequency CMN-DBS improve generalised seizures reducing intensive care time.•CMN-DBS could potentially help to avoid serious side effects srSE medication.•Low reduce severity and focal/multifocal seizures. Super refractory status epilepticus (srSE) refers SE that fails respond 1st 2nd line treatments persists after 24 hours anaesthesia carrying increased risk mortality, morbidity, disability. Centromedian Thalamic Nucleus (CMN DBS) appears provide some benefit in epilepsy [1Valentin A. Garcia Navarrete E. Chelvarajah R. Torres C. Navas M. Vico L. et al.Deep brain stimulation the centromedian nucleus for generalized frontal epilepsies.Epilepsia. 2013; 54: 1823-1833Crossref PubMed Scopus (125) Google Scholar, 2Velasco F. Velasco Jiménez A.L. Brito Rise al.Predictors difficult-to-control by electrical nucleus.Neurosurgery. 2000; 47 (discussion -5): 295-304Crossref (137) Scholar], but its efficacy best parameters this condition remain unclear. We report case 15-year-old right-handed girl with normal development no family history epilepsy. Bilateral tonic-clonic (BTCS) started at age 5 leading Paediatric Intensive Care Unit (PICU) admission thiopentone coma induction. The possibility hemophagocytic lymphohistiocytosis/macrophage activation syndrome (MAS) was raised she discharged 4 weeks later on levetiracetam, steroids cyclosporine cognitive, language behavioural difficulties. She developed brief asymmetric tonic occasional clusters 20–30 seizures/day. Multiple AEDs (phenytoin, carbamazepine, lacosamide, lamotrigine, perampanel, zonisamide, stiripentol) ketogenic diet provided limited benefit. A second occurred aged 9 6-week PICU further regression cognition. Following discharge, had significant sleep issues daytime focal unresponsiveness. Brain MRI normal. An extensive presurgical work-up scalp telemetry, PET scan ictal-SPECT suggested multiple potential epileptogenic regions excluded suitability surgery VNS implantation. 3rd 14, uncontrolled, up 30 seizures/hour, requiring PICU. Thiopentone several other drugs (felbamate, stiripentol, IVIG, steroids, anakinra, cannabinoids) were unhelpful. Most left head-eye deviation flickering 1 minute, followed arm stiffening. also clonic elements BTCS. Respiratory depression caused infections high drug doses complicated her condition. Repeat telemetry showed ictal onset over left/midline parietal region, right anterior quadrant build-up activity. After 80 days transferred King’s College Hospital (KCH) CMN implantation an attempt terminate srSE. New Clinical Procedure Committee approved technique, informed consent. (Medtronic 3389 electrodes- (Fig. 1A,B) activated date bipolar contact negative, 2 positive, 130Hz, 90 μs, 1.5 mA. initial minor improvement seizure frequency, control worsened changed simulation contacts 0, 1, negatives, 3 60Hz, 3V. Electrode impedance checked each parameter adjustment. 12-h pause clinical deterioration from bilateral 1C). re-started same increa se intensity 5V. As remained almost continuous, 48 6Hz, 300 No clear artefacts or recruitment rhythm noted EEG any 1E). days, decreased significantly more alert, enjoying uninterrupted seizure-free periods. HDU paediatric ward 17th day. Seizures midline region without spreading anteriorly. On 22nd day, pattern noted, set 60Hz/90 μs during night 6Hz/300 daytime, re-emergence 5–6 seizures/hour 1C) Based prominent activity implantation, review area possible cortical dysplasia region. Stereo-EEG (SEEG) exploration agreed switched off 27th before depth electrodes. Detailed description SEEG strategy is out scope letter recorded electrographic temporoparietal Resection led than 90% reduction patient home rehabilitation plan. Neuropathology possible, non-conclusive, dysplasia. patients super-refractory epilepticus. Seven cases have been reported describing (Table 1-supplementary material). timing variable (28–59 days) ideal target has not established. In three cases, implanted thalamus absence [[3]Lee C.Y. Lim S.N. Wu T. Lee S.T. Successful using nuclei deep stimulation.World neurosurgery. 2017; 99: 14-18Crossref (18) convulsive [[4]Yuan Zhang S. Liang Liu N. Yu X. Deep epilepticus.Epileptic Disord : international journal videotape. 2019; 21: 379-384PubMed Scholar] non-convulsive rSE[[5]Imbach L.L. Baumann C.R. Poryazova Geissler O. Brugger P. Sarnthein J. al.Anticonvulsive effect crucially depends active zone-A single observation.Seizure. 71: 286-288Abstract Full Text PDF (5) Scholar]. four targeted either due common immunodeficiency-associated encephalomyelitis [[6]Lehtimaki K. Langsjo J.W. Ollikainen Heinonen H. Mottonen Tahtinen al.Successful management stimulation.Ann Neurol. 81: 142-146Crossref (20) encephalitis (autoimmune/infectious) cardiac arrest [[7]Valentin Nguyen H.Q. Skupenova A.M. Agirre-Arrizubieta Z. Jewell Mullatti al.Centromedian epilepticus.Brain Stimul. 2012; 5: 594-598Abstract (25) febrile infection-related (FIRES) [[8]Sa Singh Pujar D’Arco Desai Eltze Anakinra FIRES - two different outcomes.Eur J Paediatr 23: 749-754Abstract (24) previous KCH one another institution terminated vegetative state probably hypoxic-ischaemic injury case, prolonged case. these outcomes, earlier time permanent neurological injury. There lack consensus regarding parameters. High-frequency (130Hz [4Yuan 8Sa , 145Hz [3Lee 5Imbach 180Hz 70–90 pulse width) appeared effective seizures, successfully resolving 1). Occasionally, evolves frequent multifocal order burden low-frequency (6Hz, μs) tried previously [7Valentin our patient, period 5–10 (Graph Other variations such monopolar/bipolar, current/voltage continuous/discontinuous properly studied cases. One hypothesis apparent are functionally connected fronto-parietal structures cortex [[9]Martin-Lopez D. Jimenez-Jimenez Cabanes-Martinez Selway R.P. Valentin Alarcon G. role versus epilepsy: evidence human recordings assessed stimulation.Int Neural Syst. 27: 1750010Crossref (13) cause highly-synchronized activity, facilitating inhibitory mechanisms which involved termination [[10]Walker M.C. epilepticus.Epilepsia. 2011; 52: 61-63Crossref (10) Continuous may disrupt generation regions, number and/or summary, life-threatening standard therapeutic option. controlling option substantially time, limiting medication, preventing damage. Low-frequency additional AV, EH, RS HH designed IS, CR DJJ reviewed analysed seizures’ data. IS AV wrote manuscript prepared graph. All authors final version manuscript. received honorarium lectures consultancy Medtronic Ltd. rest declare they competing interests. This work supported Epilepsy Research UK (grant number: P1503 ) jointly grant both Action Medical Great Ormond Street Children’s charity GN2380 ).