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Catatonic Coma With Profound Bradycardia

Received March 17, 2006; revised July 14, 2006; accepted July 26, 2006. From the Dept. of Psychiatry, Massachusetts General Hospital, Boston, MA, and the Dept. of Psychiatry, Duke University, Durham, NC. Send correspondence and reprint requests to Oliver Freudenreich, M.D., MGH Schizophrenia Program, Freedom Trail Clinic, 25 Staniford St., 2nd Fl., Boston, MA 02114. e-mail: ofreudenreich{at}partners.org

ABSTRACT

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Catatonia may be monosymptomatic at presentation, with stupor or coma as the cardinal and only manifestation. A case of catatonic coma with profound bradycardia is presented to help clinicians recognize this entity and include catatonia in the differential diagnosis of coma as a rare etiology after other more common causes of coma have been excluded. Cases of catatonic coma are nevertheless important to identify because treatment with intravenous benzodiazepines is simple and highly effective. The authors argue that the descriptive term "catatonic coma" is preferable over terms implying psychogenesis, such as "psychogenic" or "hysterical" coma; for catatonia, the authors have a specific treatment, in the form of benzodiazepines; for "psychogenesis," there is none.

INTRODUCTION

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Not all patients with altered levels of consciousness in the form of a stupor or coma suffer from a medical or neurological illness. Rarely, stupor or coma results from "nonorganic" causes, receiving various labels, depending on the theoretical orientation of the practitioners. In such cases of "psychogenic unresponsiveness," as Plum and Posner¹ call it, an attempt is made to differentiate between what is thought to be "psychological" (conversion phenomena) and more "biological" (catatonia). There is only a small literature on psychogenic coma, mainly reports in the anesthesia literature describing postoperative states in which women were typically not waking up as expected after surgery.^2–5 In a non-postoperative setting, Baxter and White⁶ recently described the case of a 20-year-old man who became unresponsive over the course of a few hours, having a Glasgow Coma Scale (GCS) score of 3. This patient resisted eye-opening and showed fluttering eyelids when his eyelashes were brushed. He had experienced a series of psychosocial stressors before the event. An uncle of the patient had had a period of similar unresponsiveness for a few days before his wedding. Because of the apparent proximity with psychosocial stress, the authors used the diagnosis of "coma due to dissociative disorder, not otherwise specified." Bender and Feutrill⁷ proposed the term "comatoid catatonia" to best describe another patient with a GCS score of 3 and flaccid muscle tone, who was thought to have a form of catatonia, even though his clinical picture matched that of a comatose patient; this patient responded well to electroconvulsive therapy (ECT).

We present a case of a patient with known schizophrenia who developed a coma-like clinical picture with profound bradycardia that responded to intravenous benzodiazepines. To our knowledge, such a catatonic coma with profound bradycardia has not been described. Our case alerts clinicians to considering a catatonic syndrome manifesting with dramatic unresponsiveness yet minimal ancillary symptoms of catatonia after more common and life-threatening etiologies of coma have been ruled out. We will make a case for the use of the descriptive term catatonic coma (or stupor for less severe cases) over terms that imply psychogenesis or mechanism of conversion, such as "dissociative coma" or "psychogenic stupor." To guide clinical practice, we advance a heuristic teaching vehicle, the "automotive model of catatonia."

Case Report

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"Mr. A," a 27-year-old man with a known history of paranoid schizophrenia, came by himself to the emergency department (ED) and complained about "slowing down" and hallucinations. His prescribed outpatient medications were olanzapine and thiothixene, but he was suspected of not taking them regularly. Haloperidol 5 mg and Cogentin 2 mg were given in the ED, but no benzodiazepine. One hour after admission to the inpatient unit, he became immobile and mute. Because his heart rate decreased to 40 bpm, he was transferred to the ICU. Of note, the patient had had a similar episode 1 year before the current episode, while taking the same regimen of olanzapine and thiothixene. Past medical history was significant for head trauma of unclear severity and "polysubstance abuse." Screening laboratory values were unremarkable.

On exam in the ICU, the patient was lying in bed with his eyes closed. He was afebrile, with a stable, regular heart rate of 40 bpm and normal blood pressure. No spontaneous movements were observed. He did not respond to commands or painful stimuli. His GCS score was 3. His pupils were small, reactive, and symmetrical, with normal reflexes to light; eyes rolled upward when eyelids were opened against minimal resistance. Motor exam showed flaccid muscle tone and normal reflexes; there was no waxy flexibility; there was no resistance to being moved except the aforementioned resistance to eye-opening. When his arm was stretched out above his head, it fell down slowly, missing his face.

Treatment in the form of a slowly administered intravenous (IV) benzodiazepine was initiated by the psychiatric team. There was no response to 2 mg lorazepam IV. A second dose of 2 mg lorazepam 5 minutes later led to yawning and some eye movements behind closed eyes. A third dose of 2 mg lorazepam was given after another 10 minutes had elapsed. The patient yawned again, started to move his legs, started to answer questions, initially with his eyes closed; but he then opened his eyes. Thus, the total dose of IV lorazepam given was 6 mg over 15 minutes. The patient was mildly psychotic but was able to relate his history of feeling slowed-down up to the point when he became nonresponsive. He was continued on 1 mg lorazepam tid, and haloperidol 5 mg qhs was added.

Discussion

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This case report illustrates several clinical points. The differential diagnosis of coma includes a rare etiology: catatonia. Catatonia as a psychiatric coma cause can be suspected in stuporous/comatose patients after the common medical/neurological etiologies have been considered and ruled out. Catatonia in this setting can be accompanied by significant bradycardia that resolves once the catatonia resolves. As opposed to the low-dose benzodiazepine regimens often suggested for catatonia, surprisingly high total doses might have to be given in repeated doses (e.g., 2 mg lorazepam or an equivalent dose of another benzodiazepine every 10 minutes), with the appropriate respiratory precautions, until the patient wakes up, confirming a diagnosis of catatonia. This is a challenge: giving a sedating agent to a comatose-appearing patient seems counterintuitive and will require some explaining to the medical/surgical team. We suspect that insufficient treatment of catatonia is often provided because of the trepidation that comes from giving high-dose benzodiazepines to a "calm" patient. We wonder whether an initially aggressive approach would be better in many cases, because it holds the potential for preventing descent into catatonic immobility. Of note, high-dose benzodiazepines should only be given in settings that are prepared to deal with the complication of a respiratory arrest. This is particularly important if other medications (such as the patient’s olanzapine) could work synergistically with benzodiazepines and increase the risk for profound respiratory depression. Patients on clozapine clearly have a higher risk for such a complication,⁸ and we recommend a most cautious approach.

The most helpful feature in this case was the patient’s past history: the subacute development of catatonia in a man known to have schizophrenia and a previous, similar episode of nonresponsiveness. Because this typical and convincing history was available, no further work-up was done. Instead, the definitive first-line treatment for catatonia was administered, given a favorable risk:benefit profile in this patient. As stated earlier, a more cautious approach and an aggressive pursuit of differential diagnosis and work-up are generally preferable. We do not advocate taking "shortcuts" and putting psychiatric causes of coma on the same level of importance with potentially life-threatening causes of coma. In this case, one can reasonably argue that an electroencephalogram (EEG) should have been obtained, particularly so as not to miss the possibility of subclinical seizure state. The differential diagnosis for this case is rather lengthy, as stuporous states are common in many medical or neurological disorders, particular delirium. Akinetic mutism and coma vigil can be confused with catatonic stupor.⁹ Both were ruled out by the absence of history, the examination, and the patient’s response to treatment. A psychiatric differential diagnosis includes "brief dissociative stupor," as outlined by Alexander et al.¹⁰ However, stupor and coma are generally used to indicate a somewhat longer period of unresponsiveness.

An EEG is abnormal in over 43% of patients with catatonia but is less likely to be abnormal in patients with a history of psychiatric illness. The presence of abnormalities is more likely in patients older than age 40 and in those with neuroleptic malignant syndrome (NMS) or the presence of general-medical conditions associated with the onset of the catatonia.¹¹ In a series of 29 patients with acute catatonia, 4 (13.8%) were found to have seizures, 2 had viral encephalitis, 1 had NMS, and 1 had schizophrenia.¹² Without an EEG, we cannot rule out the possibility of some variant of status epilepticus, which would have responded to benzodiazepines. Indeed, even patients with known psychiatric disorders may have nonconvulsive status epilepticus, and, in certain cases, lorazepam can suppress catatonia-like signs without fully terminating the underlying seizure.¹³ Thus, an EEG to rule out status epilepticus should be considered, especially if there is any question regarding the clinical history.

Should This Patient Be Considered Catatonic?
Current criteria for the presence of the catatonic syndrome are unsatisfactory in this case. When is an unresponsive and mute patient without ancillary catatonic symptoms catatonic as opposed to comatose? Modern proposed criteria for catatonia require the presence of several signs and symptoms,¹⁴ but it remains unresolved how many criteria are required to declare a catatonic syndrome to be present. Benegal and colleagues¹⁵ compared a group of patients with stupor-only (defined as some degree of mutism or some degree of motor unresponsiveness) with a group of patients who displayed classic catatonic signs, as well. The groups were comparable on demographic and clinical characteristics and treatment responses. This suggests that stupor, by itself, can be a catatonic sign sufficient to qualify a patient for a diagnosis of catatonic syndrome. Extreme cases of catatonic stupor might be catatonic coma or comatoid catatonia, given that stupor and coma lie on a continuum.

Bradycardia is not usually mentioned in the literature on catatonia. Takahashi and Gjessing¹⁶ report paradoxical bradycardia during REM sleep in periodic catatonia. Parry and colleagues¹⁷ describe the case of recurrent sinus arrest in a young schizophrenia patient with catatonia in the setting of NMS; the patient required temporary external pacing. The relationship between NMS and catatonia remains controversial, although many researchers now agree that NMS is a drug-induced form of malignant catatonia.^18,19 Our patient had none of the symptoms that are usually considered necessary for a diagnosis of typical NMS: he had no autonomic instability, no fever, and no motor rigidity. Our patient’s muscle tone was not classically catatonic, although he may have certainly had a neuroleptic-induced catatonia, given his pre-neuroleptic psychomotor retardation and worsening after haloperidol. Nevertheless, neuroleptic-induced catatonias, including NMS, from atypical antipsychotics (olanzapine had been prescribed to our patient) can lead to a modified clinical presentation without rigidity, albeit typical presentations with rigidity are far more common.^20,21

The treatment response argues strongly for catatonia. Catatonic symptoms respond rather well and at times even dramatically to intravenously-administered benzodiazepines, as was initially shown for lorazepam²² and diazepam.²³ These results have been confirmed in many later reports, and benzodiazepines are the mainstay of treatment for catatonia. The now largely historical amytal interview for "hysterical stupor" was most likely effective for states of catatonia because barbiturates and benzodiazepines share the same GABA_A agonist action.

Should This Patient Be Considered to Have Catatonia or "Psychogenic Coma?"
The panoply of terms used (e.g., dissociative stupor/coma, comatoid catatonia, akinetic catatonia, psychogenic stupor, functional coma, hysterical coma, conversion coma, nonorganic coma, pseudocoma) underscores the idea that our current understanding of the catatonic syndrome is limited, depending on the setting in which a patient is encountered and the theoretical framework applied. Historically, there has been the suggestion that some patients can become overwhelmed and immobile for psychological reasons. The language speaks of persons who become "stiff with fear," reminiscent of animals who "play dead" in response to an overwhelming situation. In animals, this "death feign" condition is often accompanied by bradycardia.

The induction of a disease-state by psychological routes is well known, ranging from depression after a loss to the rare "funeral mania."²⁴ Thus, the "reactive" nature of these states does not invalidate a catatonic condition. The psychological environment alters brain biology and can cause a disorder of motivation and movement, as catatonia, just as a primary physiological brain abnormality can. We suggest following Taylor and Fink’s classification of catatonia by considering what has been called "psychogenic coma" to be one of the catatonic syndromes that can be induced by extreme mental states (in which case the catatonia might be considered secondary).¹⁴ Catatonic coma can result from other psychiatric illnesses (e.g., catatonia in the setting of schizophrenia or bipolar illness) or from a neurological or medical illness. Finally, it can arise in and of itself (one of the rare primary catatonic syndromes such as periodic catatonia). Regardless of etiology, the catatonic state can be reversed with benzodiazepines or ECT. Catatonia secondary to schizophrenia may be somewhat more resistant to benzodiazepine treatment. The NMDA antagonists amantadine and memantine have been used with some success in such cases.^25,26

The "Automotive" Model of Catatonia
One of us (JPM) has proposed an "automotive" model of catatonia. The "engine" of the patient with catatonia is running, but the "driver" is not driving in a normal manner. The "clutch" engages the drive train in odd ways, that reflect either reverse (negativism) or forward (excessive cooperation) "gears," without regard to understandable purposes. Occasionally, the "gas pedal" is compressed vigorously (excitement). In the case presented here, the patient remained "in neutral" for an extended period. Benzodiazepines awaken the driver, who begins to use the clutch and gears in more understandable ways.

The automotive model metaphor of catatonia fits with the disturbance of the basal ganglia-thalamo-cortical circuits in catatonia and its pharmacological treatment.²⁷ The beauty of benzodiazepine treatment in catatonia is that it does not only inhibit corticostriatal tracts and decrease NMDA activity in the dorsal striatum through GABA_A activation in the medial orbitofrontal, anterior cingulate, and prefrontal cortices, but it can also disinhibit dopamine cell activity in the basal ganglia via GABA_A activation, with subsequent reduction of GABA_B inhibition of dopamine cell bodies.²⁷ Thus, benzodiazepines can work both on a "stuck driver" and a "stuck clutch," depending on the etiology of the particular catatonia.

To summarize, some cases of catatonia might be monosymptomatic, with stupor or coma being the cardinal and only manifestation. Although rare, recognition and correct management of the syndrome of catatonic coma is essential because the treatment is simple and effective, and the patient can be protected from unnecessary tests and the medical morbidity that accompanies delay. However, a catatonic coma should only be considered after a full work-up has excluded treatable medical causes, including subclinical seizure states. We discourage the term "psychogenic" to describe catatonic states; the patient cannot "will away" the motor inhibition once it has developed, regardless of etiology, although there may be cycles of withdrawal and excitement. Importantly, a label of "psychogenic" might bias the treatment team against medical intervention. For "psychogenesis," no treatment is available; for catatonia, an effective and specific treatment can be administered. Therefore, we prefer the terms "catatonic stupor" and "catatonic coma," depending on the level of unresponsiveness. These terms do not further cement the mind–body dichotomy, but merely represent the facts about the condition: a stuporous or coma-like state that results from a disorder of the termination of motor inhibition (catatonia). Other authors⁷ have suggested the term "comatoid catatonia," which seems equally appropriate when a comatose level has been reached. Either designation adds "catatonia" to the differential diagnosis of coma, and "coma" to the list of catatonic signs. Last, future reports of catatonic patients should include heart rate data in addition to a description of the typical catatonic signs and symptoms.

REFERENCES

TOP ABSTRACT INTRODUCTION Case Report Discussion REFERENCES

 

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This article has been cited by other articles:

				N. Ahuja and A. J. Lloyd On Catatonia, Seizures, and Bradycardia Psychosomatics, February 1, 2008; 49(1): 86 - 86. [Full Text] [PDF]

Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via HighWire Citing Articles via Google Scholar Articles by Freudenreich, O. Articles by Fricchione, G. L. Search for Related Content PubMed Citation Articles by Freudenreich, O. Articles by Fricchione, G. L. Other Neuropsychiatric Disorders Schizophrenia Spectrum Disorders Syndromes Secondary to General Medical Disorders

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