Abstract
To the Editor:
One of the difficulties in defining catatonia is that the term has been used to describe an acute and malignant condition in patients with multiple diagnoses, a more chronic condition, and sometimes as a manifestation of a negative outcome of a particular diagnosis. For example Wing and Shah (2006) studied catatonia in children with autism and found symptoms that included: a) increased slowness affecting movement and verbal responses; b) difficulty in initiating and completing actions; c) increased reliance on physical or verbal prompting by others; and d) increased passivity and apparent lack of motivation (Wing and Shah 2000). Since the review by Pataki in 1992, catatonia has been recognized as a condition in its own right with an acute presentation with motor symptoms, delirium, and dysregulation of multiple fundamental life support systems (Pataki et al. 1992). There were 43 reports of pediatric catatonia in the world literature in 1991, and diagnoses in these cases include multiple psychiatric syndromes including mood disorders(Pataki et al. 1992), schizophrenia, and autism (Kinrys and Logan 2001; Cohen et al. 1999). In the adult literature, we were able to identify case reports of catatonia in patients with lupus (Ditmore et al. 1992), hyperthyroidism (Farah and McCall 1995), and during psychiatric illness during pregnancy (Ferrill et al. 1992). It is therefore possible that catatonia may occur during psychiatric complications of other central nervous system conditions.
Catatonia occurs in adolescents but its prevalence is unknown, given that it is rare and may often go unrecognized. One group of researchers from France estimated catatonia to occur at an incidence rate of 0.16 per million per year in the general adolescent population and in 0.6% of the inpatient adolescent population (Cohen et al. 1999). However, another study from India found at least two signs of catatonia in 5.5% of their outpatient population (Thakur et al. 2003). This range in prevalence reflects the confusion in the early literature between catatonia as a malignant and life threatening episode, and catatonia as an ongoing form of schizophenia or a chronic condition.
The Bush-Francis Catatonia Rating Scale (BFCSR) was first developed in 1996 and can be used to evaluate the severity of its presentation (Fink 2009). The BFCRS 23 item scale is scored from 0 to 3 for each item. In order to facilitate screening for the disorder a shorter version, the Bush-Francis Catatonia Screening Instrument (BFCSI) (14 items) was also developed (Bush et al. 1996). Although the authors suggest that one to four items suggests a positive diagnosis, it is not possible to generate a cut-off score psychometrically given the rarity of the condition and lack of a diagnostic gold standard. The full 23-item BFCRS can be obtained by clinicians for use in practice in the original article (Bush et al. 1996).
The BFCRS was later revised (BFCRS-R), shortened to 20 items, and psychometrically tested using Rasch analysis (Wong et al. 2007). This study found catatonia to be a unidimensional diagnosis, again pointing to the validity of catatonia as a diagnosis in its own right. The authors note that because of the rarity of the condition, any rating scale would be insufficient to define a cut-off score for catatonia in a specific population.
ECT can be a life-saving and relatively safe treatment for catatonia in adults (Kelly and Zisselman 2000), and a number of individual case studies and chart review studies have reported the successful treatment of catatonia with ECT in adolescents beginning in 1999 (Zaw et al. 1999), with individual and case series of similar results following since that time (Singerman and Raheja 1994; Wing and Shah 2006). This is true for catatonia associated with schizophrenia (Baeza et al. 2004), mood disorders (Singerman and Raheja 1994; Pataki et al.1992) and a wide range of other conditions, including epilepsy and encephalitis (Cohen et al. 1999). Cohen et al. (1999) reviewed all English and French reports on adolescent catatonia between 1977 and 1997 and concluded that catatonia is a rare but severe disorder, which has a variety of diagnoses associated with its presentation. Furthermore, the researchers found ECT was the treatment of choice for catatonic depression and an effective secondary treatment option for catatonic schizophrenia. Researchers have also found ECT to be effective in treating neuroleptic malignant syndrome in children and adolescents (Silva et al. 1999). Rey and Walter (1997) reviewed 60 reports of ECT used in adolescents (396 cases in total) and found rates of improvement for catatonia of 80%. Serious side effects were rare, and minor side effects, the most common being headache, were brief in duration. In summary two treatments have been systematically found to be safe and effective in the literature: benzodiazepines (Taylor and Fink 2003) and/or ECT (Petrides et al. 1997).
The body of research reviewed here consists of case reports or case series. There has been a relative lack of attention to the disorder in more recent years (Cohen et al. 1999; Wachtel et al. 2008). Continued reports of catatonia and current treatment would ultimately enable a meta-analysis that might provide more systematic information. At the British Columbia Children's Hospital, we did a retrospective chart review of all the cases treated in our inpatient units with the diagnosis of catatonia over the past two decades. Here we report on the four cases identified, with the objective of determining what they had in common in order to begin the process of better defining not only the presentation but the response to treatment.
Case Presentations
Case One: CL
CL presented for admission as a 13-year-old female who had a brief psychotic episode lasting three days. She felt stressed by school and had periods of mutism, auditory and visual hallucinations, disorientation, and loosening of associations of acute onset. There was no past psychiatric history. Prior to admission she was described as a perfectionistic, “A” student, and had shown exceptional talent in music and sports. She had a strong set of close friends. At home there was conflict with her mother fairly typical for a first-generation Asian adolescent who wanted the freedoms of her Caucasian friends. She was very close to her father. Family psychiatric history was positive for what was described as a brief psychotic episode in the father, which was treated with Chinese medicine. His description of the history was difficult to interpret, but the symptoms appeared to indicate a bipolar disorder. He noted that he had experienced manageable ongoing minor difficulties with mood regulation, but he had no recurrent psychosis since that time and never missed work due to these difficulties. He described himself as very close to his daughter and noted she was aware of his mood difficulties.
Upon admission CL was treated with risperidone 1 mg and paroxetine 20 mg for what was considered a psychotic depression. A family therapy session was followed by out of control agitation and crying leading to rapid tranquilization with chlorpromazine 50 mg and diphenhydramine 25 mg. Shortly after, the nurse monitoring her noted she had increased temperature, pulse, and blood pressure. Within an hour she became rigid and unresponsive with waxy flexibility. This deteriorated further as she refused food or water, became agitated, needed restraint, and was delirious. She was incontinent. The diagnosis at that time was neuroleptic malignant syndrome and risperidone was discontinued. She did not improve and was transferred to the pediatric intensive care unit (ICU). In a state of extreme agitation she managed to remove her physical restraints, pulled out her IV, and ran through the ward screaming without any clothes, all of which was distinctly out of character. Her medical condition in the ICU continued to deteriorate dramatically. She failed to respond to benzodiazepines and required continuous hydration and restraint. She remained extremely agitated, with a creatine phosphokinase (CPK) level of 593. Lorazepam in doses up to 14 mg led to brief periods of calming but no further improvement. While in the ICU she had extensive medical work up with no abnormalities, except for elevated CPK (muscle fraction included). No BFCRS was done as this scale was not available until 1996. Neurology noted abnormal papillary response and nystagmus but no other evidence of medical abnormality.
The family was aware she was quite ill, and a process of consent for ECT was initiated through translation. They agreed to the procedure, which was initiated immediately. The first bilateral ECT was followed by a return to eating, drinking, and sleeping. The second ECT, given the next day, was followed by a decrease in agitation and rigidity. She had four more bilateral ECT treatments and was eventually completely euthymic with a completely normal mental status. She had little or no memory for what had occurred. She was discharged on olanzapine 10 mg and valproate 375 mg for the Christmas break but was readmitted shortly thereafter with confusion, paranoia, agitation, the return of psychotic symptoms, and what appeared to be early-onset catatonic agitation. The medication was held constant, and she was again booked for ECT. She had a total of 12 treatments.
She was recontacted 14 months later to determine her outcome, given the seriousness of her previous condition. At that point she was only on olanzepine 2.5 mg. She had full social, academic, and family functioning and was again doing exceptionally well in all aspects of her life. She had only a hazy memory of having been in the ICU or having been seriously ill and when asked about this seemed unsure about what had happened.
Case Two: BW
BW was a 16-year-old male who lived with his mother in a large urban center. He was diagnosed with developmental delay and autism at age 5. At the time of admission he was placed in a life skills class in high school and was able to carry out basic activities of daily living. BW was initially admitted to hospital for auditory hallucinations and paranoia, along with lack of response, refusing of food and drink, echolalia and fluctuations in blood pressure, pulse and temperature. His BFCSR score on the 23-item scale at that time was 28. He was given lorazepam 15 mg, and his BFCSR score dropped to 6, but he continued to have residual lack of reponsiveness, postural rigidity, and lack of spontaneity. Lorazepam 15 mg was maintained post discharge.
BW was readmitted to hospital shortly after discharge due to disturbed sleep, auditory hallucinations, paranoid and persecutory ideation towards his mother, agitation and restlessness, disorientation, and increased goal-directed behavior, such as compulsive cleaning. On the second day of admission he demonstrated long episodes of lack of response and maintained a fixed and rigid posture. He was refusing food, echolalic, echopraxic, and responding to auditory hallucinations. His BFCRS 23-item score was 28. In addition, a mental status exam revealed the limited speech that was present to be echolalic, aprosadic, unresponsive, and nonspontaneous. His posture was intermittently rigid, particularly when he was unresponsive. His blood pressure (BP) and pulse were fluctuating with BP up to 190/95, heart rate 170, and temperature 39.2, when agitated. BW was diagnosed with catatonia. Lorazepam was again titrated to 15mg per day, his catatonic symptoms improved, and his BFCRS score decreased to 6. All laboratory tests taken at this time were normal, expect for elevated CPK and mildly abnormal liver functioning.
During his hospitalization, medication trials included risperidone 3 mg, quetiapine 800 mg, and olanzapine 15 mg with minimal response of his psychotic symptoms. Lorazepam 15 mg was maintained as any decrease resulted in re-emergence of catatonia. Although he had a partial response to lorazepam with intermittent return of some symptoms, discharge on lorazepam 15 mg after the failure of the first admission without was treatment with ECT considered risky. After three treatments of bilateral ECT, BW showed decided improvement. After seven biweekly ECT treatments, BW had complete remission of his catatonic and psychotic symptoms and was observed by his mother to be approximating his pre-morbid state. He therefore had a total of 15 ECT treatments with no evidence of memory loss. BW was discharged on aripriprazole 15 mg and lorazepam 1 mg. At one year postdischarge BW continued to be symptom free. He had returned to pre-morbid functioning in regards to school, extracurricular activities, and his relationships. He discontinued lorazepam and his aripriprazole was titrated down slowly due to sedation.
Case Three: AM
AM was a 13-year-old female who lived with her mother, father, and two younger brothers. Prior to being admitted to the hospital, AM had a four-month history of increasing social isolation and gesturing as well as decreasing verbal output. She was also preoccupied, smiling, giggling, grimacing, muttering, and staring blankly. She had limited ability to complete activities of daily living, impaired concentration, lethargy, and a lack of interest in previously enjoyed activities.
She was admitted to the inpatient unit at BC Children's Hospital and diagnosed by the treating psychiatrist with “schizophrenia catatonic subtype” and generalized social phobia. She was also assessed to have word-finding difficulties and auditory memory problems. Her physical exam and laboratory investigations were normal, and she was prescribed a combination of quetiapine and risperidone. Discharge during the Christmas break was followed by readmission due to a lack of eating, sleeping, and refusal to communicate. After readmission, AM rapidly became immobile, catatonic, confused, anxious, and physically combative. She refused oral intake and her affect was flat. She required an IV and a nasogastric tube. Full medical and laboratory work up was negative with the exception of a CPK of 197.
She was started on a trial of oral olanzepine 5 mg and lorazepam 5 mg intravenously with no improvement. AM underwent three unilateral ECT treatments within one week with some improvement but became negativistic, mute, and agitated within a day of ECT being discontinued. After her first two treatments, she was noted to have fluctuations in vital signs, including a respiratory rate of 38, a pulse of 150 and BP of 150/90, fever, and sedation. At that point she was diagnosed as having catatonia and not NMS since neuroleptics had been discontinued during the first course of ECT. When the patient again became catatonic as evidenced by negativism, mutism, refusal of oral intake, and an inability to swallow her saliva it was decided that a full course of unilateral ECT would be initiated. She was given two or three unilateral ECT per week over a three-month period. All test results were within normal ranges. Following fifteen bilateral ECT, the catatonia remitted completely. She was initiated on loxazapine 175 mg. She was verbal and no longer confused but had mild ataxia, impaired attention, and rapid thoughts.
After the course of ECT treatment following discharge, AM gradually decompensated over the period of a month. She was negativistic, defensive, combative, attending to internal stimuli, confused, and afraid. She also refused oral intake and was unable to eliminate waste without assistance. ECT was once again initiated, and AM received sixteen more treatments of bilateral ECT at a rate of three per week. This third course of bilateral ECT again led to remission of both catatonia and psychosis, but was complicated by short-term memory and cognitive difficulties, which improved gradually. She was discharged on loxazapine 175 mg and venlafaxine extended release 150 mg. The patient had a total of 28 ECT treatments among the three admissions.
Six months later, AM was again admitted to hospital after a six-week decompensation in the community. She was paranoid, agitated, aggressive, and had auditory hallucinations but did not have any catatonic symptoms. Her appetite, sleep, and energy were normal. Her affect was flat, and she was irritable and tearful. Her problem solving and planning abilities remained limited. Her loxazapine was increased, venlafaxine decreased, and she was discharged.
At a 22-month post-ECT follow-up, AM was being managed on loxazapine 200 mg. She was functioning well and had no hallucinations or anxiety. Catatonia did not recur.
Case Four: SM
SM was a 16-year-old male in grade 11 who lived with his parents and older brother. He had a prior diagnosis of autism. Before his admission he had been struggling academically and had recently transitioned to a new group of friends who were involved in substance use and truancy. Over the previous year there was a decline in family interaction, school achievement, interests, sleep, and energy as well as an increase in irritability.
SM was brought to the emergency due to an acute onset of agitation, nonresponsiveness, confusion, disorientation, hallucinations, paranoia, and delusions. He tried to escape and was sedated. SM became confused and echolalic. He was staring blankly, cringing, and gesturing. He was also not verbalizing with limited responsiveness and lack of eye contact. He was not sleeping and admitted to suicidal ideation when responsive. Laboratory tests revealed no significant findings other than elevated white blood cell count and neutrophils. He was admitted to neurology prior to transfer to psychiatry because of reported loss of consciousness. However, a full medical work up including renal, cardiac, diabetic and neurological investigation was negative with the exception of a CPK of 1317. Vitals were BP 182/94 and pulse 109. Drug screen was negative.
On admission to psychiatry SM was diagnosed with psychotic disorder not otherwise specified with catatonia. He was treated with risperidone 1.5 mg/day. In order to manage the catatonia, he was referred for ECT and received eight bilateral ECT treatments over 3 weeks. After the first treatment, he had increased eye contact and verbalization. Previous fluctuations in his BP and pulse (BP 110/50; pulse 100) had now stabilized. Following the second ECT, he was answering questions, following commands, and performing goal-directed activities. His score on the BFCSR decreased from 23 to 9. SM missed his fifth treatment, and his symptoms of catatonia described earlier began to return. However, following his sixth treatment, he reported feeling better and once again seemed to be improving. He exhibited no psychosis or abnormal movements. He had a partial relapse of confusion, hypervigilance, and disorganization, which may have been psychotic or symptoms of residual catatonia. At the end of his eighth ECT treatment, he scored 2 on the BFCSR. His only side effects throughout the treatment process were mild headaches, short-term memory loss, and somnolence.
Upon discharge, SM had no agitation, paranoia, or psychosis, and his rapport was good. However, he had slight psychomotor retardation, blunted affect, and his memory, coordination, and movement were not back to baseline. He was discharged on clozapine 175 mg orally at bedtime and velafaxine extended release 150 mg orally in the morning.
Discussion
Catatonia is a rare disorder in adolescents, but can be life threatening when present. The four cases presented demonstrate common patterns of treatment. In each case, the child had psychoses comorbid with other conditions and received neuroleptic medication. This meant that the treating clinicians were initially unclear as to the differential with NMS. However, the diagnosis of NMS is ruled out given that all four cases had neuroleptics prior to, during, and following ECT and yet responded with resolution of symptoms.
Catatonia was complicated by life-threatening symptoms or confusion or true delirium, agitation, refusal to eat or drink, nonresponsiveness, fluctuating and often dangerously elevated vital signs, and intermittent motor rigidity. Although it could not be determined from the chart review, the marked fluctuations in vital signs may have been an artifact of the agitation or a reflection of the underlying condition. In each of the cases the onset was rapid and dramatic. Extensive medical work up was done in the pediatric ICU for organic conditions with numerous consultations. Work up included lumbar puncture, magnetic resonance imaging, electroencephalogram, computed tomography, and laboratory investigation including complete blood count, electrolytes, glucose, liver function tests, thyroid, ceruloplasmin, copper, selenium, Vitamin B12, folate, antinuclear antibody, and screens for porphyria, cerebral spinal fluid protein, and glucose. It should be noted that while results were pending, ECT was begun immediately, so that delay in treatment would be avoided. All of these patients required treatment in a medical or pediatric intensive care unit, depending on whether they remained at BC Children's Hospitalor had already been transferred to an adult unit for ECT. All of the cases described also had marked elevation of CPK, probably due to myolysis. Early and immediate response was noted from the first treatment for all patients, but full resolution of the catatonia was not consolidated until the patient had received a full course of treatment. The total number of ECT received for each patient was 12, 15, 28, and 8 respectively, for a mean of 17 treatments which is comparable to ECT used in other conditions.
All the patients in this series received and had a partial response to lorazepam. This raised the question for the clinician as to whether lorazepam should be held prior to ECT to assure an adequate seizure, and the decision was made to withhold lorazepam for the 12 hours prior to each seizure. Partial response to catatonia has been well recognized in the literature on ECT (Yeung et al. 1996). The other observation that is evident from these case histories is that once the catatonia resolved with ECT, in no patient did it recur (Fink 1990). A limitation of this study, apart from the small number of cases, is that for all of these patients ECT was given together with other medications, and therefore improvement could be ascribed to other causes. However, the dramatic pattern of improvement noted after each ECT, the dramatic deterioration when ECT was missed, and the eventual linear consolidation of response with continued treatment makes this unlikely.
Although ECT was associated with some memory loss in one patient, this is typical of what one sees with ECT, and such memory loss is not typically long lasting. This case series has the benefit that we were able to contact some of these patients up to more than a year postdischarge and confirm that there was no recurrence of catatonia. In none of the patients contacted for follow up was there any residual memory loss, apart from memory of what had transpired during the episode itself.
In order to obtain adequate support for these patients, they were transferred to the ICU and then transported by ambulance or transferred to an adult hospital for ECT. Many child inpatient units do not have access to ECT on site, but this brief case series should increase awareness that ECT may represent a relatively benign and possibly life-saving treatment where medication or support fail in cases of malignant catatonia in adolescents (Fink 1990). From this case series, and consistent with all the literature on catatonia in previous reports, this is an illness that has a dramatic onset, has the potential to be life threatening, is responsive to very high doses of lorazepam, at least in the short term, (Petrides et al.1997), and can be safely and effectively treated with ECT, often with complete remission.
Footnotes
Disclosures
Blake Allan and Muffy Greenaway have no conflicts of interest or financial ties to report. Dr. Weiss has received unrestricted educational grants from Shire, Eli Lilly, Purdue and Janssen Ortho. Dr Weiss has been on the speakers board or advisory board and/or been a consultant for Eli Lilly, Shire, Purdue, Janssen, Novartis, Takeda, and Abbot. She has also received royalties from Johns Hopkins University Press and Checkmate Plus.