EEG and video documentation of benzodiazepine challenge in catatonic stupor: A case report

Abstract

Introduction

Catatonia, a psychomotor disorder characterized by diverse clinical signs, including stupor and mutism, remains elusive in its causes and a challenge to diagnose. Moreover, it is often underrecognized due to its resemblance to disorders of consciousness. However, when diagnosing catatonia, an antipsychotic medication may exacerbate the condition. The first‐line treatment typically includes benzodiazepines and/or electroconvulsive therapy (ECT).

Case Report

A 60‐year‐old woman with systemic lupus erythematosus (SLE) and epilepsy presented with catatonic stupor. Despite stable treatment, she experienced an acute deterioration in consciousness, requiring hospitalization. Her condition improved markedly following a benzodiazepine challenge, as documented on EEG. This improvement was short‐lived, but a second benzodiazepine challenge restored her from E1V1M1 (stupor) to E4V5M6 within minutes, as documented by a video recording. The patient was treated with lorazepam 1.5 mg/day orally and did not experience further relapses.

Discussion

The diagnosis of catatonia had been based on her scores on the Bush‐Francis Catatonia Rating Scale (BFCRS; Screening, 6/14; Severity, 19), despite meeting only two DSM‐5 criteria for catatonia (stupor and mutism). The diagnosis was supported by EEG and video documentation, excluding other potential differential diagnoses such as nonconvulsive status epilepticus and encephalopathy. Additional quantitative EEG analyses indicated that benzodiazepine administration increased brainwide alpha and beta band power significantly, suggesting that the benzodiazepine normalized attention, consciousness, and long‐range synchronization. This report additionally emphasizes the significance of video recordings in managing catatonia, and it helps in accurately tracking symptoms, documenting comprehensively, and improving patient understanding, which is crucial for treatment adherence.

This case report describes the rapid improvement of a female patient with unspecified catatonia (DSM‐5) after a benzodiazepine challenge. A video recording was useful for multidisciplinary collaboration and patient and early career doctor education. Although evidence of pre‐ and‐post‐EEG comparisons in benzodiazepine challenge is limited, this case report suggests that conducting comparisons even within normal limits may be beneficial.

1. INTRODUCTION

Catatonia is a psychomotor disorder manifesting diverse clinical signs, including stupor, mutism, negativism, ambitendency, stereotypy, posturing, waxy flexibility, and echophenomena. ¹ Although it was documented in “Die Catatonie” by Kahlbaum in 1874, the underlying causes and mechanisms remain elusive. ² , ³ Despite its history and clinical significance, the identity of catatonia continues to be a contentious topic in the Diagnostic and Statistical Manual of Mental Disorders (DSM). Catatonia was historically conceived as a type of schizophrenia, but other psychiatric illnesses can cause catatonia. ⁴ Additionally, recent research has shown that its underlying causes are often physical illnesses including NMDA receptor encephalitis, acute infectious diseases, and multiple sclerosis. ¹ , ⁴ , ⁵ Clinically, catatonia often mimics disorders of consciousness. This complicates its diagnosis and leads to frequent underrecognition. Diagnosing catatonia is essential, as antipsychotic medications may exacerbate the condition ⁵ and first‐line treatments characteristically include benzodiazepines and/or electroconvulsive therapy (ECT). ¹ , ⁵ Although, the diagnostic test accuracy of EEG is increasingly recognized as determining the etiology of catatonia, ⁴ with blood and imaging examinations, no single examination can conclusively diagnose or exclude catatonia and its etiology. Moreover, it remains unclear as to which EEG findings might indicate a higher likelihood of response to benzodiazepine treatment, irrespective of etiology. Here we present a patient with a catatonic stupor improved by benzodiazepine challenges. We quantify how a benzodiazepine may alter an EEG that appears initially to be within normal limits and how these changes correspond to clinical improvements. We will discuss the importance of EEG and video documentation in catatonia management.

2. METHODS

For EEG analysis, 8 periods of 14 s each (approximately 2 min) were extracted both pre‐ and postdiazepam administration. The spectral components using Fast Fourier Transform (FFT) were characterized as a previous study ⁶ with slight modifications. Briefly, power/frequency was visualized using a periodogram based on FFT and divided into delta, theta, alpha, beta, and gamma bands. ⁷ The pre‐ and postpower values were statistically compared (Detailed in Methods S1).

3. CASE PRESENTATION

A 60‐year‐old woman with systemic lupus erythematosus (SLE) and epilepsy experienced gradual anhedonia over 2 weeks and insomnia for 3 days without any discernable psychological causes. She had two episodes of repetitive neuropsychiatric SLE (NPSLE) in the past, which required methylprednisolone pulse therapy 12 years ago and 2.5 years ago (7 months and 2 months of hospitalization, respectively). During her first hospitalization, she was diagnosed with epilepsy. She had been managing both her SLE and epilepsy well for years with prednisolone 3 mg/day, azathioprine 50 mg/day, hydroxychloroquine 200 mg/day, valproate 500 mg/day, and perampanel 6 mg/day. Although she had gone shopping with her family the day before admission, her consciousness deteriorated abruptly, and she was transferred to a university hospital. At the emergency department, her Glasgow Coma Scale was E4V1M2. Her temperature was 38.6°C, and her blood pressure was 179/89 mmHg. Comprehensive examinations, including blood and cerebrospinal fluid analyses, cranial MRI, and culture examinations, revealed no significant findings. On day 2, the patient exhibited symptoms including stupor, mutism, staring, rigidity, and withdrawal. She remained in a semi‐sitting position for long periods without reacting. Her consciousness deteriorated to E1V1M1, requiring a benzodiazepine challenge under EEG monitoring. The initial low‐amplitude basic activity with rare α waves on EEG (Figure 1A) improved remarkably to 40–60 μV α waves (Figure 1B) promptly after diazepam was administered intravenously (Figure 1C), and her status improved to E4V5M6. Although she relapsed on day 3, a second benzodiazepine challenge restored her from E1V1M1 (stupor) to E4V5M6 within minutes and this was video recorded (Video S1; Figure 1D,E). She was subsequently treated with lorazepam 1.5 mg/day orally. After confirming the need for ongoing lorazepam medication with the help of the video recording, she was discharged without recurrence on day 13. Her cognitive function was assessed with a score of 30 on the Mini‐Mental State Examination (MMSE) during her outpatient visit on day 27, and there were no subsequent relapses.

FIGURE 1.

EEG and Level of Consciousness Before‐and‐After Benzodiazepine Administration. (A) Initial EEG showing low‐amplitude basic activity with rare α waves. (B) Improvement to 40–60 μV α waves observed promptly after administering 5 mg diazepam intravenously (C) Density Spectral Array (DSA) illustrating EEG changes before‐and‐after benzodiazepine administration. (D) On day 4, a video‐documented benzodiazepine challenge restored her from E1V1M1 (stupor) to (E) E4V5M6 within minutes (See Video S1).

4. DISCUSSION

4.1. Diagnosis of catatonia

To diagnose catatonia, it is crucial to exclude any disorders of consciousness caused by medical conditions such as NPSLE, nonconvulsive status epilepticus (NCSE), and encephalopathy/encephalitis. Even when catatonia is diagnosed, “catatonic disorder due to another medical condition” should be distinguished. However, the causal relationship between medical conditions and catatonia is often difficult to conclude.

Certain autoimmune antibodies, such as anti‐phospholipid, anti‐NMDA receptor, and anti‐ribosomal P protein antibodies, have been associated with SLE and neuropsychiatric symptoms. ⁸ However, since this patient had no abnormalities in her cerebrospinal fluid analysis, including in her protein and IL‐6 levels, and she recovered successfully with the benzodiazepines, we decided not to measure these antibody levels in a shared decision‐making process with the patient. Furthermore, the EEG‐documented benzodiazepine challenge and neuroimaging effectively supported the exclusion of NCSE and encephalopathy/encephalitis in this patient. Additionally, the patient did not meet the DSM‐5 criteria for neurodevelopmental, psychotic, bipolar, depressive, or other mental disorders, and no triggering psychological events were identified for the dissociative stupor.

She was diagnosed with “unspecified catatonia” based on DSM‐5 since she manifested only stupor and mutism (2 out of 12 items). However, her diagnosis was confirmed as catatonia based on the Bush‐Francis Catatonia Rating Scale (BFCRS; Screening, 6/14; Severity, 19), which boasts good reliability. ⁹ Notable discrepancies included staring, rigidity, and withdrawal, as previously reported. ⁹ A previous report revealed that of the 232 validated catatonia cases (BFCRS ≥2 and treatment responsive), 211 (91%) met DSM‐IV criteria, whereas only 170 (73%) satisfied DSM‐5 criteria for catatonia. ⁹ Therefore, physicians and psychiatrists should assess catatonia with the BFCRS, even if the patient meets two or fewer criteria of the DSM‐5, to recognize potentially treatment‐responsive patients. Furthermore, EEG and/or video‐documented benzodiazepine challenge examination is recommended.

4.2. Mechanism of catatonia and quantitative analysis of EEG

Existing hypotheses have postulated that catatonia involves the motor system, particularly hyperactivity in the supplementary motor area (SMA) and pre‐SMA, which is crucial for motor control and influenced by the neurotransmitter GABA. ⁵ These hypotheses are supported by the response to benzodiazepines (GABA receptor agonists) and mECT treatments. Functional assessment is typically conducted using nuclear imaging studies with a temporal resolution of hours. Combining this with EEG, which has a better temporal resolution (~seconds to minutes), is worthwhile to illustrate rapid clinical improvement.

A recent meta‐analysis emphasized the significance of electroencephalogram (EEG) in identifying the underlying causes of catatonia, demonstrating a sensitivity of 0.82 (95% CI 0.67–0.91) and a specificity of 0.66 (95% CI 0.45–0.82) for detecting a medical etiology of the condition. ⁴ Previously reported EEG abnormalities included features of encephalopathy or limbic encephalitis, epileptiform discharges, focal abnormality, and status epilepticus. ⁴ EEG findings in patients with “Catatonia associated with another mental disorder” or “unspecified catatonia” have shown an increase in frequency and a decrease in amplitude of alpha waves during catatonic stupor. ¹⁰ Among schizophrenia subtypes, the catatonic type is reported to present “choppy” records, that is, low voltage fast activity, more frequently than other subtypes. ¹¹ Notably, these patterns are considered “within normal limit.” No studies have quantitatively compared EEG findings before‐and‐after benzodiazepine challenge.

In this case, the initial EEG was normal and consistent with the reported findings, showing low voltage alpha and fast waves. However, the EEG after the benzodiazepine challenge showed increased voltage of alpha and beta bands (Figure 1). Due to the limited literature on EEG changes following benzodiazepine challenges, additional analyses were conducted in this study.

EEG before‐and‐after benzodiazepine administration was segmented into delta, theta, alpha, beta, and gamma frequency bands. The findings suggested that benzodiazepine administration leads to an increase in power across all frequencies, with robust and statistically significant increases particularly in the alpha and beta bands (Figure 2). This pattern was consistently observed across various electrode placements (Figure 3), indicating that attention, consciousness, and long‐range synchronization ⁷ were broadly normalized by benzodiazepine administration.

FIGURE 2.

Quantitative EEG Analysis Before‐and‐After Benzodiazepine Administration. (A) Eight segments, each 14 seconds long (totaling approximately 2 min), were extracted both before‐and‐after diazepam administration. (B) Representative EEG from O1 electrode before administration (B‐1), Power/Frequency using a periodogram based on Fast Fourier Transformation (B‐2), and spectrogram (B‐3). (C) Post‐administration EEG from the same O1 electrode (C‐1), Power/Frequency (C‐2), and spectrogram (C‐3). (D) Pre‐and‐post power values are divided into delta (1–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), beta (13–30 Hz), and gamma (30–45 Hz) bands, and statistically compared (black, pre; red, post). An enlarged view of the area enclosed in (D‐1) is shown in (D‐2). Theta, alpha, and beta bands are significantly different (p = 0.022, p < 0.0001, p < 0.0001, respectively).

FIGURE 3.

Comparative power values across electrodes. Theta, alpha, beta, and gamma band power values in all electrodes are shown. Consistent statistical significance in alpha and beta bands' pre‐ and postdifferences is noted; however, electrode‐specific trends are not discernible. p‐values are denoted as * <0.05, **<0.01, and ***<0.001. Delta bands are omitted due to artifacts from eye movements that cannot be removed automatically.

The preliminary quantitative analyses suggest that EEG could be a useful real‐world dynamic brain marker, although individual variability should be considered. EEG‐documented benzodiazepine challenges are recommended when there is a discrepancy between the clinical symptoms and the EEG findings, even when the EEG is within normal limits. Collecting dynamic before‐and‐after data in this context may reveal a promising avenue for future research and clinical assessment.

4.3. Video recording advantages

Video recordings played a crucial role in determining and explaining the treatment approach in this case. Due to a history of severe complications from past methylprednisolone pulse therapy, physicians and psychiatrists agreed to avoid increasing immunosuppressive drugs. Instead, the priority was to prescribe lorazepam if benzodiazepine rapidly improved her condition.

Video recordings offer three pivotal advantages:

1. Objective evidence and tracking temporal recovery course: Video enables reliable documentation of progressively fluctuating neural symptoms, which may be subject to high interrater differences. Repeatedly reviewable video facilitates collaborative and multidisciplinary assessments by physicians and psychiatrists.

2. Minimizing oversight of symptoms: Engaging with patients might divert attention to facial symptoms, overlooking others, such as extremity myoclonus. Video ensures comprehensive symptom capture.

3. Explanatory Tool: Patients' comprehension of their condition, vital for sustained pharmacotherapy or even illness stability, can be enhanced through sufficient explanation and video demonstrations. ¹² , ¹³ Since catatonic stupor is an involuntary condition and patients frequently do not remember the worst period, a video recording may be used as an explanatory tool, which may increase treatment adherence.

5. CONCLUSION

Catatonic stupor can be dramatically improved within minutes following effective treatment. EEG and video documentation of benzodiazepine challenges provide objective evidence and a promising dynamic brain marker, reduce symptom oversight, and serve as an explanatory tool for patient comprehension and treatment adherence, as concurrently used with exhaustive examinations of underlying pathologies by other modalities.

AUTHOR CONTRIBUTIONS

HT, YTs, SS, DT, YTa, and NT treated the patient. HT analyzed the EEG data, edited the video, and drafted the first manuscript. TK supervised the project. All authors proofread and approved the final manuscript.

FUNDING INFORMATION

Next Generation Biomedical Measurement Research Network Program, The University of Tokyo supported by Nakatani Foundation, Japan (H.T.), and Research grant by Juntendo University (H.T.).

CONFLICT OF INTEREST STATEMENT

TK reports grants from Sumitomo‐Pharma outside the submitted work. The other authors have no conflicts of interest to disclose.

ETHICS STATEMENT

Informed Consent: Written informed consent was obtained (Detailed in Supplementary Information).

Registry and the Registration No. of the study/trial: N/A.

Approval of the research protocol by an Institutional Reviewer Board: N/A.

Supporting information

Data S1.

Tamune H, Tsukioka Y, Sakuma S, Taira D, Takaoka Y, Tamura N, et al. EEG and video documentation of benzodiazepine challenge in catatonic stupor: A case report. Neuropsychopharmacol Rep. 2024;44:468–473. 10.1002/npr2.12427

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available in the supplementary material of this article.