HHS Public Access Author manuscript Author Manuscript Psychosomatics. Author manuscript; available in PMC 2019 May 02. Published in final edited form as: Psychosomatics. 2018 ; 59(3): 302–305. doi:10.1016/j.psym.2017.10.004. Targeted Electroconvulsive Therapy for Super Refractory Status Epilepticus: A Case Report and Literature Review Dana M. Pinchotti, D.O., Department of Psychiatry, University of New Mexico, Albuquerque, NM Author Manuscript Christopher Abbott, M.D., and Department of Psychiatry, University of New Mexico, Albuquerque, NM; R01: ECT current amplitude and medial temporal lobe engagement, 1R01MH111826 MRN COBRE II Project 5: Multimodal Imaging of Neuropsychiatric Disorders (MIND): Mechanisms & Biomarkers (COBRE II), 5P20GM103472, Albuquerque, NM Davin K. Quinn, M.D. Department of Psychiatry, University of New Mexico, Albuquerque, NM; 2P20-GM109089-O1A1, The UNM Center for Brain Recovery and Repair, Albuquerque, NM Introduction Author Manuscript Electroconvulsive therapy (ECT) has been shown to be effective for a number of medical conditions that manifest in a general hospital, including malignant catatonia, neuroleptic malignant syndrome, toxic delirium, and status epilepticus. Although over 20 case reports suggest that ECT may be effective in cases of medically intractable status epilepticus, it is a rarely used treatment. We present a case of a patient with drug-resistant epilepsia partialis continua persisting for 51 days before ECT was successfully implemented and discuss the theory and practice of ECT for status epilepticus. Case Report Author Manuscript Mr. J, a 51-year-old man with severe alcohol use disorder, presented to the emergency department (ED) in January 2015 with new-onset status epilepticus, first manifesting with generalized tonic-clonic seizures, then progressing to right-sided focal motor seizures of the upper extremity and face. Computed tomography (CT) scan demonstrated a new anteriorinferior left temporal lobe hemorrhagic parenchymal contusion, presumably due to repeated falls. After 8 days, resolution of epileptiform activity on electroencephalogram (EEG) was achieved after the administration of lacosamide, levetiracetam, phenytoin, and midazolam. On the day of discharge, Mr. J’s EEG continued to show mild-to-moderate diffuse slowing in the left hemisphere. He was discharged on hospital day 14 on levetiracetam 1000 mg bid, phenytoin 300 mg bid, and lacosamide 100 mg bid. Send correspondence and reprint requests to Dana Pinchotti, D.O., University of New Mexico, Albuquerque, NM, 87131-1466; dpinchotti@salud.unm.edu. Pinchotti et al. Page 2 Author Manuscript Mr. J then presented to the ED in early March of 2015 after being found down with right upper extremity and right side facial twitching after reportedly missing his anticonvulsants that day. On initial examination, Mr. J was noted to be awake but mute, with diminished muscle strength in the right-sided extremities and continued right-side facial twitching. Laboratory values revealed no underlying cause, and magnetic resonance imaging (MRI) showed only the previous left hemorrhagic temporal lobe contusion. He was administered lorazepam 5 mg and phenytoin 800 mg but the seizures persisted. He was transferred to the Neuroscience ICU where he was loaded with phenytoin 1100 mg, lacosamide 400 mg, and levetiracetam 4000 mg over the next 24 hours. Author Manuscript Mr. J continued with seizure over the next several days, leading to intubation and administration of midazolam, lorazepam, valproic acid, and topiramate. Despite trials of multiple first- and second-line agents, the EEG continued to demonstrate focal motor status emanating from the left hemisphere, with additional epileptogenic cerebral dysfunction arising from the left frontal regions of the hemisphere. By hospital day (HD) 10, Mr. J was placed in a pentobarbital coma for burst suppression. For the next month, status epilepticus persisted, despite trials of ketamine (13,586 mg daily), felbamate (2800 mg daily), zonisamide (200 mg daily), methyprednisolone (1000 mg daily), carbamazepine (1800 mg daily), perampanel (12 mg daily), and an experimental neurosteroid medication, allopregnanolone. Brain positron emission tomography (PET) showed evolving hypermetabolic ictal focus over the left lateral and middle temporal lobes, areas essential to speech and motor function, rendering Mr. J a nonsurgical candidate. By HD 50, at the suggestion of the neurology team, his family agreed to a trial of ECT for seizure control. Both the psychiatry and neurology teams participated in the consenting process. Author Manuscript From days 52–54, the patient received a total of 9 bitemporal and 2 bifrontoparietal ECT treatments (Table 1A). The Thymatron System IV machine was used for all treatments, utilizing 900 mA current amplitude, 1.0 ms pulse width, pulse frequency 70 Hz, train duration 8 seconds, total charge 504 millicoulombs. Maximum device output (100% energy) was employed given previous literature and the number of anticonvulsants in vivo at the time of stimulation. Prior to each treatment series, oral and intravenous anticonvulsants were held, flumazenil was used to reverse benzodiazepine effects, glycopyrrolate was given to avoid prolonged asystole from repeated nonconvulsive stimulations, and a nondepolarizing neuromuscular blocking agent was used to prevent stimulation-induced muscle contractions and hyperkalemia (rocuronium and vecuronium). Video EEG monitoring was temporarily discontinued during each session, to avoid potential damage to the EEG amplifiers from the ECT. Motor seizure activity was monitored using the cuff method on the left leg. Author Manuscript Only 1 out of 6 stimulations produced a detectable seizure on HD 52. Therefore, Mr. J was weaned off of pentobarbital during the subsequent ECT treatments, with midazolam utilized for burst suppression. On HD 53, 2 out of 3 stimulations produced seizures of 47 and 12 seconds’ duration. On HD 54, a bifrontoparietal electrode montage was utilized, based on the hypothesis that application of the stimulus closer to the frontal motor strip seizure focus might lead to increased anticonvulsant effect in that area. Two out of 2 stimulations produced robust seizures of 87 and 89 seconds, presumably owing to the taper of pentobarbital (Table 1B). Psychosomatics. Author manuscript; available in PMC 2019 May 02. Pinchotti et al. Page 3 Author Manuscript Author Manuscript Following the eleventh ECT treatment, Mr. J had a distinct change on continuous EEG monitoring, from diffuse beta waves intermixed with alpha waves from benzodiazepine effects, to paroxysmal theta activity with maximum electronegative focus over the left anterior and middle temporal lobe. At first there was concern that ECT had worsened the seizure activity, prompting cessation of the treatments. However, 3 days post-ECT treatment, the background EEG pattern improved, and the patient had spontaneous eye opening. Clobazam was then initiated. One week following ECT, Mr. J exhibited eye tracking, and after the second week, he was responding to commands. Seventeen days after ECT treatment, he had no seizure activity on EEG. On HD 96, Mr. J was discharged to a longterm rehabilitation facility. At the time of discharge, he was able to verbalize short phrases. More than 1 year later, he demonstrated no further episodes of status epilepticus and progressed to verbalizing full sentences. He remains on his discharge medication regimen: lacosamide 300 mg bid, levetiracetam 3000 mg bid, clobazam 20 mg bid, phenytoin 225 mg tid, and carbamazepine 600 mg tid. Discussion Author Manuscript One of the indications for ECT, as specified by the American Psychiatric Association, is intractable seizures.1 A recent systematic review of 19 cases of ECT in status epilepticus found that 57% reported improvement, but the level of evidence supporting ECT for status is generally poor.2 Two subsequent case reports documented successful use of ECT for status epilepticus in a 16-year-old cerebral palsy patient and a 4-year-old patient with FIRES (febrile infection-related epilepsy syndrome).3,4 We acknowledge that in this literature, it is difficult to ascertain whether cessation of status after ECT is a result of the ECT itself, due to spontaneous recovery, or due to simultaneous therapies. Rarely is status broken immediately following electroconvulsive stimulation. However, we believe our case is a clear example of how ECT contributed to cessation of status when extensive medical therapy alone failed. The temporal relationship between the changes of EEG seizure characteristics suggests that the ECT treatments were integral in the evolution of the status and the patient’s response to medication. This case was also unique for its individualized electrode placement targeting the seizure focus to increase efficacy, a technique that is gaining ground as both invasive and noninvasive forms of brain stimulation move toward tailored delivery of electromagnetic energy to functional brain abnormalities.5 Theory of Anticonvulsant Effect of ECT Author Manuscript Although the exact mechanism of ECT is unknown, several known consequences of ECT suggest how it may be beneficial in seizure disorders. First, it is well established that seizures occur as a result of abnormal excessive or synchronous neuronal activity in the brain.6 The possible anticonvulsant effects of ECT may be due to direct or indirect neurotransmitter alterations that diminish aberrant neuronal activity. Glutamate is transiently increased after a motor and EEG seizure, followed by an increase in gamma-aminobutyric acid (GABA), leading to overall increased cortical inhibition.7 Evidence suggests that cortical GABA concentration can increase twofold following a single course of ECT.8 Furthermore, ECT not only produces increases in GABA but also resets the ratio of inhibitory to excitatory stimulus.9 This might provide an explanation as to why the patient’s Psychosomatics. Author manuscript; available in PMC 2019 May 02. Pinchotti et al. Page 4 Author Manuscript EEG transiently worsened following ECT but eventually progressed to resolution of the status. Author Manuscript Second, while convulsions are known to be an important component of the ECT effect, there is ample evidence showing that electrode placement and parameters of electrical stimulation modulate both efficacy and side effects. In our case, it is reasonable to wonder if the placement of electrodes over the area of seizure focus facilitated beneficial changes preferentially in that region. Mr. J′s SE was assumed to be a result of his chronic subdural hematoma, which resulted in an area of hypermetabolic potential epileptogenic focus. Although the ECT stimulus itself was clearly excitatory (causing seizure), its metabolic and vascular postictal effects induced at or near the epileptogenic zone may have reduced neuronal excitability and firing. There is an initial ictal increase in cerebral blood flow and metabolism in ECT, followed by longer-term decreases in blood flow after multiple treatments, all of which may have contributed to neuronal stabilization.10 Furthermore, his EEG changed significantly after the last 2 treatments employing the targeted montage, progressing to paroxysmal theta waves in the left temporal region, a possible reflection of regional functional change. This theory is supported by effects seen with transcranial magnetic stimulation (TMS) delivered to seizure foci in intractable epilepsy, in which seizure pauses and lasting seizure reductions have been observed directly after TMS pulses.5 Third, trophic downstream consequences of ECT include bilateral increases in regional cortical thickness, increases in glial cells, and increases in inhibitory GABAergic interneurons.11 However, it is not clear how these physiologic changes might contribute to the anticonvulsant effect. Practical Application of ECT for Status Epilepticus Author Manuscript Author Manuscript When providing ECT for status epilepticus, consultant psychiatrists should be mindful of the following modifications to typical ECT procedures: (1) The neurology team should be involved in the consenting procedure, and ideally should sign the consent form with the ECT provider, as the ECT is being done for a neurological rather than psychiatric indication. (2) Discontinuation of unhelpful anticonvulsants and temporary cessation of all anticonvulsant medications before the procedure will help make ECT-induced seizures more robust. (3) Precautions to prevent over-saturation or damage to video or continuous EEG amplifiers during ECT should be taken. (4) Reversal agents such as flumazenil can be helpful if benzodiazepines are part of the treatment regimen or are used for burst suppression. (5) Glycopyrrolate is recommended given the theoretical risk of asystole when ECT is performed at maximum energy in status patients. (6) Use of a nondepolarizing (vs depolarizing, i.e., succinylcholine) paralysis agent is recommended to avoid compounding the risk of hyperkalemia in bed bound patients susceptible to rhabdomyolysis. (7) There does not appear to be a benefit to minimizing the amount of charge delivered—maximum FDA-approved machine output should be used. (8) Multiple treatments in the same day are typical in these cases. Psychosomatics. Author manuscript; available in PMC 2019 May 02. Pinchotti et al. Page 5 Author Manuscript Conclusion Consultant psychiatrists will be increasingly called upon to recommend or apply noninvasive brain stimulation techniques in the general hospital. In the case of ECT for status epilepticus, more research is needed to fully comprehend the nature of its anticonvulsant effects. References Author Manuscript Author Manuscript 1. Fink M: The practice of electroconvulsive therapy: recommendations for treatment, training, and privileging. Psychiatr Serv 2002; 53(8):1040–1104 2. Zeiler FA, Matuszczak M, Teitelbaum J, Gillman LM, Kazina CJ: Electroconvulsive therapy for refractory status epilepticus: a systematic review. Seizure 2016; 35:23–32 [PubMed: 26789495] 3. Incecik F, Horoz OO, Herguner OM, Yıldızdas D, Altunbasak S: Electroconvulsive therapy for refractory status epilepticus in a child: a case report. Ann Indian Acad Neurol 2015; 18(3):364 [PubMed: 26425029] 4. Veiga AM, Moreno DC, Menéndez AI, et al.: effectiveness of electroconvulsive therapy for refractory status epilepticus in febrile infection–related epilepsy syndrome. Neuropediatrics 2017; 48(01):045–048 5. Rotenberg A, Bae EH, Takeoka M, Tormos JM, Schachter SC, Pascual-Leone A: Repetitive transcranial magnetic stimulation in the treatment of epilepsia partialis continua. Epilepsy Behav 2009; 14(1):253–257 [PubMed: 18832045] 6. Fisher RS, Boas WV, Blume W, et al.: Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005; 46(4):470–472 [PubMed: 15816939] 7. Biedermann S, Weber-Fahr W, Zheng L, et al.: Increase of hippocampal glutamate after electroconvulsive treatment: a quantitative proton MR spectroscopy study at 9.4 T in an animal model of depression. World J Biol Psychiatry 2012; 13(6):447–457 [PubMed: 21767208] 8. Sanacora G, Mason GF, Rothman DL, et al.: Increased cortical GABA concentrations in depressed patients receiving ECT. Am J Psychiatry 2003; 160(3):577–579 [PubMed: 12611844] 9. Sackeim HA, Decina P, Prohovnik I, Malitz S, Resor SR: Anticonvulsant and antidepressant properties of electroconvulsive therapy: a proposed mechanism of action. Biol psychiatry 1983; 18(11):1301–1310 [PubMed: 6317065] 10. Nobler MS, Oquendo MA, Kegeles LS, et al.: Decreased regional brain metabolism after ECT. Am J Psychiatry 2001; 158(2):305–308 [PubMed: 11156816] 11. Van Eijndhoven P, Mulders P, Kwekkeboom L, et al.: Bilateral ECT induces bilateral increases in regional cortical thickness. Transl Psychiatry 2016; 6(8):e874 [PubMed: 27552587] Author Manuscript Psychosomatics. Author manuscript; available in PMC 2019 May 02. Author Manuscript 52 52 52 52 53 53 53 54 54 5 6 7 8 9 10 11 52 2 4 52 1 3 Hospital day Bifrontoparietal Bifrontoparietal Bitemporal Bitemporal Bitemporal Bitemporal Bitemporal Bitemporal Bitemporal Bitemporal Bitemporal Lead placement 100% 100% 100% 100% 100% 100% 100% 100% 100% 100% 100% Energy administered Author Manuscript ECT treatment number Glycopyrrolate 0.4 Flumazenil 1 Vecuronium 10 Flumazenil 1 Glycopyrolate 0.4 Flumazenil 1 Rocuronium 100 Flumazenil 0.9 Glycopyrolate 0.1 Flumazenil 0.2 Rocuronium 50 Medications administered (mg) 89 87 14 12 47 No seizure No seizure 8 No seizure No seizure No seizure Length of motor seizure (seconds) Author Manuscript ECT Treatment Details 89 89 14 12 47 No seizure No seizure 10 No seizure No seizure No seizure Length of EEG seizure (seconds) Author Manuscript TABLE 1A. Pinchotti et al. Page 6 Psychosomatics. Author manuscript; available in PMC 2019 May 02. Author Manuscript Author Manuscript Yes Yes 53 54 600 600 600 600 600 600 600 600 57 58 59 60 61 62–88 89–96 600 600 800 100 Lacosamide 56 55 Yes 52 ECT 6000 6000 6000 6000 6000 6000 6000 6000 6000 6000 6000 6000 Leviteracetam 1800 1800 1800 1800 1800 1800 1800 1800 1800 1800 1800 1800 Carbamazepine 2664 2664 Pentobarbital 32 192 192 48 288 288 288 240 665 864 Midazolam 675 675 675 675 600 600 600 600 600 675 975 Fosphenytoin 40 40 40 30 Clobazam Author Manuscript Maximum Daily Dosage of Medication Used During and After ECT Hospital Day 600 Phenytoin Author Manuscript TABLE 1B. Pinchotti et al. Page 7 Psychosomatics. Author manuscript; available in PMC 2019 May 02.