Use of En-Bloc Multiple Monitored Electroconvulsive Therapy in Benzodiazepine Refractory Malignant Catatonia

Abstract

We report a case of an adolescent female experiencing benzodiazepine and single-stimulation electroconvulsive (ECT) refractory malignant catatonia, who improved with the use multiple monitored ECT (mmECT). Per the 2001 American Psychiatric Association guidelines, mmECT should only be considered in cases of intractable seizures or neuroleptic malignant syndrome. Since 2001, neuroleptic malignant syndrome and malignant catatonia have been described as occurring along the same spectrum of illness. Therefore, given the life-threatening nature of her condition, as well as the brief seizure duration she experienced from single-stimulation ECT, the patient was treated with en-bloc and two-stimulation mmECT. The patient demonstrated a significant improvement in response to this treatment, with her Bush Francis Catatonia Rating Scale score decreasing by 89%. At two-year follow-up in an outpatient neurodevelopmental catatonia clinic, the patient has been able to return to school in her previous advanced placement classes and has not required maintenance ECT.

Introduction:

First described in 1966 by Blachly, multiple monitored electroconvulsive therapy (mmECT) occurs under generalized anesthesia with constant monitoring by electroencephalogram (EEG). Historically, ECT stimulations were administered between two to eight times with a three-minute interval between treatments.¹ Since 1966, there have been concerns regarding the cognitive side effect burden of mmECT, and a lack of robust studies beyond case reports/series addressing the efficacy of mmECT. In 2001, this led to the American Psychiatric Association to recommend against the widespread use of mmECT, stating that mmECT should only be considered in urgent cases of intractable seizure or neuroleptic malignant syndrome. However, recent reports have continued to document positive clinical responses to mmECT in the treatment of severe conditions.^2–4 En-bloc ECT, defined as receiving daily ECT treatments over two or more days, has also been used in the treatment of potentially life-threatening conditions such as treatment-resistant mania, psychosis with agitation, acute delirium, and catatonia.⁵ In the following case, the patient discussed presented with malignant catatonia refractory to benzodiazepines and single stimulation ECT, which responded to en-bloc mmECT.

Case Report:

Initial presentation

The patient is a 16-year-old female with a history of attention-deficit hyperactivity disorder, autism spectrum disorder (ASD), and anxiety who presented to the emergency department after one month of increasing psychosis. The child and adolescent psychiatry consult liaison service was consulted on hospital day #1. Pediatric neurology and rheumatology were also consulted as the patient’s symptoms triggered the autoimmune encephalitis clinical practice pathway in the hospital providing her care. On mental status examination, the patient demonstrated fluctuating levels of psychomotor agitation and slowing, mutism except for when responding to internal stimuli, poor eye contact with intermittent fixed gaze, and posturing which was held for the entirety of the interview. Initial labs were notable for a sedimentation rate of 1, C-reactive protein of 7.6 mg/L (0.1 – 1.7 mg/mL), and chloride of 112. A brain MRI was also completed, which demonstrated a mildly increased sulcal FLAIR hyperintensity; thought to be due to the effects of oxygen and generalized anesthesia. However, given her severe symptomology and these findings, a lumbar puncture was recommended by radiology.

Due to the patient’s inability to participate in the clinical interview, collateral was taken from her mother. Per her mother’s report, the patient was in her normal state of health until one month prior to hospitalization. She then experienced sleeplessness and rapid speech. She also experienced audiovisual hallucinations, including an unknown man she believed was speaking to her in the room. The patient had no history of similar symptoms. She was then hospitalized at an inpatient psychiatric facility outside of our health system the week before admission. The patient was discharged from this facility the day before presenting to the emergency department. After discharge, the patient left her home in the early morning hour, prompting her parents to take her to the emergency department for further evaluation.

Medical and psychiatric diagnostic workup and treatment

Initial examination by child and adolescent psychiatry consult-liaison service was significant for a Bush Francis Catatonia Rating Scale (BFCRS) score of 20. Prominent symptoms included excitement, mutism, staring, rigidity, and perseveration. The patient underwent a lorazepam challenge with 1 mg of IV lorazepam. This resulted in a significant reduction of the BFCRS score, with the patient having a BFCRS score of 6 two and a half hours after lorazepam was administered. The patient was then started on scheduled IV lorazepam 1 mg every 6 hours. On hospital day #3, she underwent a lumbar puncture which returned positive for anti- N-methyl-D-aspartate receptor antibodies; treatment with intravenous immunoglobin and steroids was initiated. On hospital day #5, the patient began showing signs of autonomic instability including tachycardia and hypertension, suggestive of malignant catatonia. Throughout her hospitalization and treatment, the patient’s peak systolic blood pressure was 150 and her peak pulse was 180.

Use of ECT in the treatment of catatonia

Due to continued catatonic symptoms along with autonomic instability, and the well documented efficacy of ECT in catatonia across the life-cycle,^6,7 an ECT consult was placed on hospital day #8, with the first ECT treatment occurring on hospital day #10. A summary of the patient’s ECT treatment can be found on Table 1. All ECT treatments were bitemporal, with the following parameters: energy of 576 mC, pulse width of 1 ms, frequency of 60 Hz, and duration of 6 seconds. Due to ongoing symptomology including an absence of oral intake requiring nasogastric tube feeds and IV hydration, sustained autonomic instability, hyperactivity resulting in harm to self and others, as well as a brief seizure duration due to high dose benzodiazepine use despite co-administration with flumazenil; mmECT was initiated on hospital day #16. Informed consent was obtained by the patient’s mother prior to treatment. Two ECT stimulations were administered if the total seizure duration of the first stimulation was under 40 seconds. If a second stimulation was administered, it was done so immediately following the cessation of seizure activity as seen on EEG. This treatment plan was followed except for treatment number ten, during which time the ECT provider deemed the first seizure adequate for treatment. Single stimulus en-bloc ECT treatments were delivered on hospital day #10 to #11, and #13 to #14. En-bloc mmECT treatments were delivered on hospital day #20 through #23, #27 through #31, as well as #35 and #36. Thus, the highest number of en-bloc mmECT treatments delivered was 5.

Table 1.

Summary of Case Report Clinical Care

Treatment Number	Duration of Hospitalization in Days	Number of ECT Stimuli	Duration of First Seizure in seconds	Duration of Second Seizure in seconds	Total Seizure Duration in seconds	Total Dosage of Flumazenil pre ECT	Total Daily Dose of Lorazepam	Total Daily Dose of Diazepam	Total Daily Dose of Memantine	Total Bush Francis Catatonia Rating Scale Score
1	10	1	10	-	10	0.2 mg	18 mg	-	-	27
2	11	1	29	-	29	0.2 mg	20 mg	-	10 mg	23
3	13	1	29	-	29	0.2 mg	22 mg	-	15 mg	-
4	14	1	17	-	17	0.2 mg	22 mg	-	15 mg	24
5	16	2	11	34	45	0.3 mg	22 mg	-	15 mg	24
6	20	2	8	12	20	0.3 mg	-	150 mg	15 mg	21
7	21	2	13	15	28	0.3 mg	-	150 mg	15 mg	18
8	22	2	6	18	24	0.3 mg	-	150 mg	15 mg	24
9	23	2	5	10	15	0.3 mg	-	150 mg	20 mg	19
10	24	1	33	-	33	0.3 mg	-	150 mg	20 mg	20
11	27	2	7	42	49	0.3 mg	-	150 mg	20 mg	19
12	28	2	8	10	18	0.3 mg	-	195 mg	20 mg	18
13	29	2	16	39	55	0.3 mg	-	195 mg	20 mg	13
14	30	2	15	8	23	0.3 mg	-	195 mg	20 mg	9
15	31	2	27	21	48	0.3 mg	-	195 mg	20 mg	9
16	35	2	36	46	82	0.3 mg	-	195 mg	20 mg	9
17	36	2	14	12	26	0.3 mg	-	195 mg	20 mg	10
18	38	2	12	35	47	0.3 mg	-	180 mg	20 mg	12
19	40	2	28	55	83	0.3 mg	-	180 mg	20 mg	14
20	44	1	23	-	23	0.3 mg	-	180 mg	20 mg	3
21	46	1	12	-	12	0.3 mg	-	180 mg	20 mg	3

Pharmacologically, on hospital day #11 memantine was initiated as an augmenting treatment. Due to ongoing severe symptomology, on hospital day #20 the patient was transitioned from lorazepam to diazepam. The maximum daily dose of lorazepam was 22 mg, reached on hospital day #16. The maximum daily dose of diazepam was 195 mg, reached on hospital day #28. The decision to transition from lorazepam to diazepam was made based on data from previous research investigating lorazepam-refractory cases of pediatric catatonia.⁸ Memantine was increased to 20 mg daily by hospital day #23. Medically, the patient’s hospitalization was complicated by a positive COVID-19 test on hospital day #17. The patient was symptomatic only for a mild cough. On hospital day #22 there was concern for seizure due to new onset upper extremity jerking which occurred intermittently over the course of ten to twenty minutes and was accompanied by worsening agitation. To further investigate, a continuous EEG was ordered. The EEG identified rhythmic delta activity which was thought to be secondary to uncommon electrographic manifestations of encephalopathy vs a subclinical seizure. As a precaution, H was placed on lacosamide, which was transitioned to oxcarbazepine 300 mg twice daily.

Overall, the patient received a total of fourteen mmECT treatments; 11 of which were scheduled en-bloc. Given the patient’s significant clinical benefit after her nineteenth ECT procedure, defined as an 89% reduction in BFCRS compared to examination upon admission, mmECT was discontinued at treatment twenty. Before her admission ended, the patient could eat on her own and participate in physical, occupational, and speech therapies. On hospital day #54, the patient was deemed medically stable for transfer to an inpatient rehabilitation hospital. At two-year follow-up in an outpatient neurodevelopmental catatonia clinic, the patient has been able to return to school in her previous advanced placement classes. Additionally, she has no residual symptoms of catatonia and has returned to her life without restrictions. The patient is no longer prescribed benzodiazepines or oxcarbazepine. The patient has also not required maintenance ECT. The patient does remain on memantine 20 mg daily as her family felt it benefited her ability to focus and concentrate in school.

Discussion:

Malignant catatonia is a life-threatening condition that is associated with a high degree of morbidity and mortality, which may be further complicated if refractory to high-dose benzodiazepines. In this case, the patient’s clinical presentation was also not responsive to single stimulus ECT occurring at an every two to three-day interval. Given the ongoing severity, the use of en-bloc mmECT was considered to be urgent and lifesaving.. The en-bloc schedule was also selected given its historically documented efficacy in catatonia.⁵ It is notable that the brief nature of the patient’s initial seizures may have been due to the high initial ECT stimulus being significantly over the seizure threshold, and that she would have responded clinically to a standard course of ECT. However, given the severe nature of her presentation and the co-administration of large dose benzodiazepines; high stimulus ECT was utilized from the onset of treatment. with an eventual transition to multiple stimulus administration. Overall, given the patient’s acutely worsening symptoms; a rapid response to treatment was urgently needed and was obtained with the utilization of this technique.

To our knowledge, this is the first documented use of combined en-bloc and mmECT in the treatment of catatonia. Overall, our report is notable given the significant and sustained clinical improvement experienced by our patient despite her burden of illness. If future providers are to consider en-bloc mmECT as a potential therapeutic option, given the current American Psychiatric Association 2001 recommendations of only two stimulation ECT, we would recommend the same course of action. Moreover, the American Psychiatric Association recommendations state that mmECT may be considered in cases of the neuroleptic malignant syndrome;² a condition which was once thought to be a separate entity outside of malignant catatonia, but is now considered along the same spectrum of illness.⁹ Thus, based on these recommendations and our presented case, we would recommend consideration of this technique only in the presence of life-threatening and treatment-refractory malignant catatonia or neuroleptic malignant syndrome.

Abbreviations:

mmECT

Multiple Monitored Electroconvulsive Therapy

EEG

Electroencephalogram

ASD

Autism Spectrum Disorder

BFCRS

Bush Francis Catatonia Rating Scale

Data Availability:

The raw data utilized in this study is available upon reasonable request