- Email: [email protected]
Pregnancy and malignant catatonia
General Hospital Psychiatry 29 (2007) 69 – 71
Case Reports
Pregnancy and malignant catatonia Mariana Espı´nola-Nadurille, M.D.a,4, Jesus Ramı´rez-Bermu´dez, Ph.D.a,b, Gregory L. Fricchione, M.D.c,d a Neuropsychiatry Unit, National Institute of Neurology and Neurosurgery, Mexico City 14269, Mexico Clinical Research Department, National Institute of Neurology and Neurosurgery, Mexico City 14269, Mexico c Division of Psychiatry and Medicine, Massachusetts General Hospital, Boston, MA, USA d Division of International Psychiatry, Massachusetts General Hospital, Boston, MA, USA Received 23 August 2006; accepted 2 October 2006
b
Abstract The occurrence of malignant catatonia in pregnancy is a psychiatric emergency. In this article, we present the case of a pregnant woman with a first psychotic episode with catatonic features, autonomic abnormalities and elevated creatinine phosphokinase levels in the context of a severe adverse reaction to antipsychotic pharmacotherapy who had good responses to electroconvulsive therapy and lorazepam. D 2007 Elsevier Inc. All rights reserved. Keywords: Malignant catatonia; Electroconvulsive therapy; Lorazepam; Pregnancy
1. Case report A 22-year-old woman of indigenous ethnicity from a rural Mexican region presented at 21 weeks’ gestation to the emergency room of the National Institute of Neurology and Neurosurgery of Mexico in an agitated as well as disorganized state and with restlessness, auditory and visual hallucinations and disorganized speech. When the patient was attempted to be interviewed, she did not focus her attention on the interviewer and was not responsive to commands and questions. The patient’s family stated that she came from a very poor economic status and was a victim of physical and verbal abuse by her husband. One month before her current state, the patient was involved in a car accident from which she was not physically injured and suffered no head trauma. A couple of days later, she started to behave oddly and subsequently experienced an insidious onset of a clinical state characterized by auditory and visual hallucinations, psychomotor agitation and disorganized behavior as well as speech. During that month, she did not receive treatment and was restrained at her home, where she had intermittent episodes of agitation alternating with episodes of withdrawal, mutism and refusal to take water and food. Her husband continued to abuse her physically. 4 Corresponding author. E-mail address: [email protected] (M. Espı´nola-Nadurille). 0163-8343/$ – see front matter D 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.genhosppsych.2006.10.003
On examination prior to use of antipsychotic medication, the patient’s pulse rate was 100 beats per minute, blood pressure was 140/90 mm Hg, body temperature was 378C and respiratory rate was 24 breaths per minute. She was diaphoretic and had evidence of moderate dehydration. On laboratory investigation, she had an elevated creatinine phosphokinase (CPK) level (511 IU/L) and an elevated white blood cell (WBC) count (14.4109/L). Otherwise, the results from her neurologic and general physical examinations, lumbar puncture and computerized tomography brain scan were unremarkable. In the emergency room, the patient received haloperidol (5 mg im) for the treatment of her agitation. A few hours later, she developed fluctuations in consciousness, generalized muscular rigidity, immobility, mutism, staring, negativism, waxy flexibility, withdrawal and signs of mitgehen (sign arm raising in response to light pressure of finger despite instructions to the contrary) as well as gegenhalten (resistance to passive movement that is proportional to the strength of the stimulus; appears automatic rather than willful) along with autonomic abnormalities such as a body temperature of 388C, pulse rate of 120 beats per minute and profuse diaphoresis. CPK increased to 1686 UI/L, WBC count did to 17.8109/L and serum sodium did to 152. Haloperidol was discontinued. Prerenal acute renal failure was diagnosed when elevations of urea as well as creatinine and oliguria were documented. The patient was admitted to
70
M. Espı´nola-Nadurille et al. / General Hospital Psychiatry 29 (2007) 69 – 71
the UCI, and intravenous hydration was started. After 48 h, the electrolyte imbalance was stabilized and the patient was transferred to the psychiatric unit, where she was found to have psychotic symptoms such as delusions, hallucinations and disorganized speech. All motor and systemic features had disappeared except for mild rigidity. No antipsychotic medication was started. Twenty-four hours later, the patient spontaneously developed all the catatonic features that she had presented with previously. ECT was started with no immediate response; thus, 6 h later, lorazepam therapy (1mg tid) was begun. Dramatic improvements in the agitation, rigidity, withdrawal and staring were seen 1 h after the first dose of lorazepam was administered. Mitgehen and gegenhalten signs progressively disappeared with the maintenance of oral lorazepam and electroconvulsive therapy, which was given thrice a week. Within 10 days, the patient’s CPK and WBC count returned to normal levels. She was kept in observation with no antipsychotic therapy; after a few days, auditory hallucinations with paranoid and religious systematized delusions predominated in her mental state and agitation as well as motor symptoms had remitted. She was diagnosed as having a schizophreniform disorder and was treated with clozapine because her psychotic symptoms did not respond to 10 sessions of bilateral ECT with a stimulus of 20% given with a Thymatron DGx ECT machine. Serial obstetric ultrasonography was used throughout her hospital stay to monitor the fetus, and no deleterious effect from the illness or the treatments was observed. 2. Discussion One of the challenges of this case was the diagnostic complexity that it presented. At admission to the emergency room, the distinction between an agitated psychotic state and an excited catatonia was not clear. The patient’s condition was treated as agitated psychosis; however, we now surmise that our patient was admitted to the hospital in a state of catatonic excitement. She presented with excitement, mutism, withdrawal and negativism, 4 of the 14 signs that the Bush–Francis Catatonia Rating Scale (BFCRS) defined for screening catatonia [1]. Unfortunately, her agitation led to the choice of haloperidol as a medication to control her behavior and she subsequently developed stuporous catatonia with the presence of immobility, rigidity, mutism, staring, waxy flexibility and other classic signs such as mitgehen and gegenhalten [2]. Another diagnostic issue involved classifying the severe catatonic syndrome as neuroleptic malignant syndrome (NMS), a form of malignant catatonia (MC) secondary to neuroleptic exposure. As stated, before neuroleptic treatment, the patient had presented with catatonia accompanied by mild autonomic disturbances (diaphoresis, increase in heart rate, respiratory rate, blood pressure), elevated CPK and leukocytosis. After the haloperidol intake, she developed fluctuations in consciousness and an intensified malignant catatonic syndrome (and NMS), with further
increase of CPK and WBC count as well as worsening of autonomic abnormalities and hyperthermia. It is known that NMS and MC involve a complex interaction of motor, behavioral and autonomic manifestations that share a similar pathophysiology regulated by alterations in GABAergic, dopaminergic and glutamatergic transmissions in the mesostriatal and mesocortical systems [3,4]. In the literature, it is now generally accepted that NMS is a form of MC precipitated by the use of neuroleptics and that the two conditions are one entity, in contrast to the theory that each syndrome has to be viewed as a separate disorder [5–7]. We conclude that our patient presented in a catatonic state with autonomic and biochemical features (CPK) and, after the use of neuroleptic medication, developed an intensified malignant syndrome that could have been lethal if not treated appropriately. The hypermetabolic state of pregnancy made the patient more vulnerable for dehydration and decompensation that ended in acute prerenal failure, a common complication of MC. Treatment issues are important in this case. First of all, it is very important to recognize excited catatonia before starting antipsychotic treatment; in the present case, the previous or simultaneous occurrence of mutism, negativism and indifference to the environment (including relatives and interviewer) could have oriented the therapeutic decision (i.e., the avoidance of haloperidol, which would normally be a first-line treatment in noncatatonic and agitated pregnant patients with psychotic symptoms). Atypical antipsychotics may be a better option under these circumstances. Reviewed studies show that clozapine apparently does not increase the teratogenic risk if administered to pregnant women, whereas more than a few studies suggest increased hyperglycemic risk for pregnant women related to atypical antipsychotic therapy during gestation. It is well known that the potential consequences of an untreated psychotic episode may be severe and may lead to the mother attempting suicide and/or infanticide. For these reasons, in our case, we had to weigh both fetal and neonatal risks of exposure to the atypical antipsychotic against the potential risk that the patient and her infant may incur if the psychosis was not treated. We decided in favor of the atypical antipsychotic; however, metabolic effects had to be monitored [8]. The BFCRS is a useful tool for differential diagnosis. ECT and lorazepam can be used cautiously, safely and successfully together when a pregnant patient with MC is encountered in clinical practice [9,10] The present case supports the similarities between MC and NMS and provides information related to differential diagnosis and therapeutic decision making in pregnant patients with MC. References [1] Bush G, Fink M, Petrides G, Dowling F, Francis A. Catatonia: I. Rating scale and standardized examination. Acta Psychiatr Scand 1996;93:129 – 36. [2] Kruger S, Bagby RM, Hoffler J, Braunig P. Factor analysis of the Catatonia Rating Scale and catatonic symptom distribution across four diagnostic groups. Compr Psychiatry 2003;44(6):472 – 82.
M. Espı´nola-Nadurille et al. / General Hospital Psychiatry 29 (2007) 69 – 71 [3] Caroff SN, Mann SC, Francis A, Fricchione GL, editors. Catatonia: from psychopathology to neurobiology. 1st ed. Arlington (VA): American Psychiatric Publishing; 2004. p. 111 – 7. [4] Fricchione G, Mann SC, Caroff SN. Catatonia, lethal catatonia, and neuroleptic malignant syndrome. Psychiatr Ann 2000;30: 347 – 55. [5] Fink M. Neuroleptic malignant syndrome and catatonia: one entity or two? Biol Psychiatry 1996;39:1 – 4. [6] White DA. Catatonia and the neuroleptic malignant syndrome — a single entity? Br J Psychiatry 1992;161:558 – 60.
71
[7] Fricchione G, Bush G, Fozdar M, Francis A, Fink M. Recognition and treatment of the catatonic syndrome. J Intensive Care Med 1997;12(3):135 – 47. [8] Gentile S. Clinical utilization of atypical antipsychotics in pregnancy and lactation. Ann Pharmacother 2004;(7–8):1265 – 71. [9] Petrides G, Divadeenam KM, Bush G, Francis A. Synergism of lorazepam and electroconvulsive therapy in the treatment of catatonia. Biol Psychiatry 1997;42(5):375 – 81. [10] Ferrill MJ, Kehoe WA, Jacisin JJ. ECT during pregnancy: physiologic and pharmacologic considerations. Convuls Ther 1992;8(3):186 – 200.
Case Reports
Pregnancy and malignant catatonia Mariana Espı´nola-Nadurille, M.D.a,4, Jesus Ramı´rez-Bermu´dez, Ph.D.a,b, Gregory L. Fricchione, M.D.c,d a Neuropsychiatry Unit, National Institute of Neurology and Neurosurgery, Mexico City 14269, Mexico Clinical Research Department, National Institute of Neurology and Neurosurgery, Mexico City 14269, Mexico c Division of Psychiatry and Medicine, Massachusetts General Hospital, Boston, MA, USA d Division of International Psychiatry, Massachusetts General Hospital, Boston, MA, USA Received 23 August 2006; accepted 2 October 2006
b
Abstract The occurrence of malignant catatonia in pregnancy is a psychiatric emergency. In this article, we present the case of a pregnant woman with a first psychotic episode with catatonic features, autonomic abnormalities and elevated creatinine phosphokinase levels in the context of a severe adverse reaction to antipsychotic pharmacotherapy who had good responses to electroconvulsive therapy and lorazepam. D 2007 Elsevier Inc. All rights reserved. Keywords: Malignant catatonia; Electroconvulsive therapy; Lorazepam; Pregnancy
1. Case report A 22-year-old woman of indigenous ethnicity from a rural Mexican region presented at 21 weeks’ gestation to the emergency room of the National Institute of Neurology and Neurosurgery of Mexico in an agitated as well as disorganized state and with restlessness, auditory and visual hallucinations and disorganized speech. When the patient was attempted to be interviewed, she did not focus her attention on the interviewer and was not responsive to commands and questions. The patient’s family stated that she came from a very poor economic status and was a victim of physical and verbal abuse by her husband. One month before her current state, the patient was involved in a car accident from which she was not physically injured and suffered no head trauma. A couple of days later, she started to behave oddly and subsequently experienced an insidious onset of a clinical state characterized by auditory and visual hallucinations, psychomotor agitation and disorganized behavior as well as speech. During that month, she did not receive treatment and was restrained at her home, where she had intermittent episodes of agitation alternating with episodes of withdrawal, mutism and refusal to take water and food. Her husband continued to abuse her physically. 4 Corresponding author. E-mail address: [email protected] (M. Espı´nola-Nadurille). 0163-8343/$ – see front matter D 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.genhosppsych.2006.10.003
On examination prior to use of antipsychotic medication, the patient’s pulse rate was 100 beats per minute, blood pressure was 140/90 mm Hg, body temperature was 378C and respiratory rate was 24 breaths per minute. She was diaphoretic and had evidence of moderate dehydration. On laboratory investigation, she had an elevated creatinine phosphokinase (CPK) level (511 IU/L) and an elevated white blood cell (WBC) count (14.4109/L). Otherwise, the results from her neurologic and general physical examinations, lumbar puncture and computerized tomography brain scan were unremarkable. In the emergency room, the patient received haloperidol (5 mg im) for the treatment of her agitation. A few hours later, she developed fluctuations in consciousness, generalized muscular rigidity, immobility, mutism, staring, negativism, waxy flexibility, withdrawal and signs of mitgehen (sign arm raising in response to light pressure of finger despite instructions to the contrary) as well as gegenhalten (resistance to passive movement that is proportional to the strength of the stimulus; appears automatic rather than willful) along with autonomic abnormalities such as a body temperature of 388C, pulse rate of 120 beats per minute and profuse diaphoresis. CPK increased to 1686 UI/L, WBC count did to 17.8109/L and serum sodium did to 152. Haloperidol was discontinued. Prerenal acute renal failure was diagnosed when elevations of urea as well as creatinine and oliguria were documented. The patient was admitted to
70
M. Espı´nola-Nadurille et al. / General Hospital Psychiatry 29 (2007) 69 – 71
the UCI, and intravenous hydration was started. After 48 h, the electrolyte imbalance was stabilized and the patient was transferred to the psychiatric unit, where she was found to have psychotic symptoms such as delusions, hallucinations and disorganized speech. All motor and systemic features had disappeared except for mild rigidity. No antipsychotic medication was started. Twenty-four hours later, the patient spontaneously developed all the catatonic features that she had presented with previously. ECT was started with no immediate response; thus, 6 h later, lorazepam therapy (1mg tid) was begun. Dramatic improvements in the agitation, rigidity, withdrawal and staring were seen 1 h after the first dose of lorazepam was administered. Mitgehen and gegenhalten signs progressively disappeared with the maintenance of oral lorazepam and electroconvulsive therapy, which was given thrice a week. Within 10 days, the patient’s CPK and WBC count returned to normal levels. She was kept in observation with no antipsychotic therapy; after a few days, auditory hallucinations with paranoid and religious systematized delusions predominated in her mental state and agitation as well as motor symptoms had remitted. She was diagnosed as having a schizophreniform disorder and was treated with clozapine because her psychotic symptoms did not respond to 10 sessions of bilateral ECT with a stimulus of 20% given with a Thymatron DGx ECT machine. Serial obstetric ultrasonography was used throughout her hospital stay to monitor the fetus, and no deleterious effect from the illness or the treatments was observed. 2. Discussion One of the challenges of this case was the diagnostic complexity that it presented. At admission to the emergency room, the distinction between an agitated psychotic state and an excited catatonia was not clear. The patient’s condition was treated as agitated psychosis; however, we now surmise that our patient was admitted to the hospital in a state of catatonic excitement. She presented with excitement, mutism, withdrawal and negativism, 4 of the 14 signs that the Bush–Francis Catatonia Rating Scale (BFCRS) defined for screening catatonia [1]. Unfortunately, her agitation led to the choice of haloperidol as a medication to control her behavior and she subsequently developed stuporous catatonia with the presence of immobility, rigidity, mutism, staring, waxy flexibility and other classic signs such as mitgehen and gegenhalten [2]. Another diagnostic issue involved classifying the severe catatonic syndrome as neuroleptic malignant syndrome (NMS), a form of malignant catatonia (MC) secondary to neuroleptic exposure. As stated, before neuroleptic treatment, the patient had presented with catatonia accompanied by mild autonomic disturbances (diaphoresis, increase in heart rate, respiratory rate, blood pressure), elevated CPK and leukocytosis. After the haloperidol intake, she developed fluctuations in consciousness and an intensified malignant catatonic syndrome (and NMS), with further
increase of CPK and WBC count as well as worsening of autonomic abnormalities and hyperthermia. It is known that NMS and MC involve a complex interaction of motor, behavioral and autonomic manifestations that share a similar pathophysiology regulated by alterations in GABAergic, dopaminergic and glutamatergic transmissions in the mesostriatal and mesocortical systems [3,4]. In the literature, it is now generally accepted that NMS is a form of MC precipitated by the use of neuroleptics and that the two conditions are one entity, in contrast to the theory that each syndrome has to be viewed as a separate disorder [5–7]. We conclude that our patient presented in a catatonic state with autonomic and biochemical features (CPK) and, after the use of neuroleptic medication, developed an intensified malignant syndrome that could have been lethal if not treated appropriately. The hypermetabolic state of pregnancy made the patient more vulnerable for dehydration and decompensation that ended in acute prerenal failure, a common complication of MC. Treatment issues are important in this case. First of all, it is very important to recognize excited catatonia before starting antipsychotic treatment; in the present case, the previous or simultaneous occurrence of mutism, negativism and indifference to the environment (including relatives and interviewer) could have oriented the therapeutic decision (i.e., the avoidance of haloperidol, which would normally be a first-line treatment in noncatatonic and agitated pregnant patients with psychotic symptoms). Atypical antipsychotics may be a better option under these circumstances. Reviewed studies show that clozapine apparently does not increase the teratogenic risk if administered to pregnant women, whereas more than a few studies suggest increased hyperglycemic risk for pregnant women related to atypical antipsychotic therapy during gestation. It is well known that the potential consequences of an untreated psychotic episode may be severe and may lead to the mother attempting suicide and/or infanticide. For these reasons, in our case, we had to weigh both fetal and neonatal risks of exposure to the atypical antipsychotic against the potential risk that the patient and her infant may incur if the psychosis was not treated. We decided in favor of the atypical antipsychotic; however, metabolic effects had to be monitored [8]. The BFCRS is a useful tool for differential diagnosis. ECT and lorazepam can be used cautiously, safely and successfully together when a pregnant patient with MC is encountered in clinical practice [9,10] The present case supports the similarities between MC and NMS and provides information related to differential diagnosis and therapeutic decision making in pregnant patients with MC. References [1] Bush G, Fink M, Petrides G, Dowling F, Francis A. Catatonia: I. Rating scale and standardized examination. Acta Psychiatr Scand 1996;93:129 – 36. [2] Kruger S, Bagby RM, Hoffler J, Braunig P. Factor analysis of the Catatonia Rating Scale and catatonic symptom distribution across four diagnostic groups. Compr Psychiatry 2003;44(6):472 – 82.
M. Espı´nola-Nadurille et al. / General Hospital Psychiatry 29 (2007) 69 – 71 [3] Caroff SN, Mann SC, Francis A, Fricchione GL, editors. Catatonia: from psychopathology to neurobiology. 1st ed. Arlington (VA): American Psychiatric Publishing; 2004. p. 111 – 7. [4] Fricchione G, Mann SC, Caroff SN. Catatonia, lethal catatonia, and neuroleptic malignant syndrome. Psychiatr Ann 2000;30: 347 – 55. [5] Fink M. Neuroleptic malignant syndrome and catatonia: one entity or two? Biol Psychiatry 1996;39:1 – 4. [6] White DA. Catatonia and the neuroleptic malignant syndrome — a single entity? Br J Psychiatry 1992;161:558 – 60.
71
[7] Fricchione G, Bush G, Fozdar M, Francis A, Fink M. Recognition and treatment of the catatonic syndrome. J Intensive Care Med 1997;12(3):135 – 47. [8] Gentile S. Clinical utilization of atypical antipsychotics in pregnancy and lactation. Ann Pharmacother 2004;(7–8):1265 – 71. [9] Petrides G, Divadeenam KM, Bush G, Francis A. Synergism of lorazepam and electroconvulsive therapy in the treatment of catatonia. Biol Psychiatry 1997;42(5):375 – 81. [10] Ferrill MJ, Kehoe WA, Jacisin JJ. ECT during pregnancy: physiologic and pharmacologic considerations. Convuls Ther 1992;8(3):186 – 200.