Abstract
Chief Complaint and Presenting Problem
History of Present Illness
According to her mother and aunt, S. started acting abnormally about a week and a half prior to her admission. As had been the case for approximately the past three years, the week prior to her menses was characterized by S.'s increased mood lability and odd behavior, which included inappropriate laughter, tearfulness, and internal preoccupation. In the past, these episodes had lasted two to three days, and her outpatient pediatrician had prescribed clonazepam 0.125 mg as needed when this occurred. The family reported that this had not been helpful in the past, and the few doses given currently were ineffective as well. Mother reported that S.'s symptoms worsened, and she became more dysphoric and agitated and began talking to herself loudly. When mother inquired as to what was bothering her, S. proclaimed that she had been ridiculed at school by her teacher for her poor singing abilities. When mother asked the teachers what had happened, they had no knowledge of the incident, but noted that S. had been more irritable recently. Over the next few days, S. became more upset and hyperverbal. She refused to eat or drink, refused assistance with brushing her teeth and bathing herself, and had an entire night where she did not fall asleep, shouting to herself, seemingly nonsensically. The next day, mother took S. to an emergency department where she was evaluated, told to discontinue the clonazepam, and sent home. Her symptoms subsequently worsened; she began referring to herself by a different name and repeating phrases such as “test, test one, two.” She reportedly became hostile toward her mother, insisting that she was not her real mother. S. eventually became aggressive, which was entirely out of character for her, pulling mother's hair and swatting at her younger siblings, insisting that her entire family was not her real family. Mother took S. to the emergency department of a different hospital, where S. was evaluated by both the pediatric neurology and pediatric psychiatry consultation services.
S. was initially evaluated by a neurologist who noted that she was awake and alert, but was not oriented to person, place, or time. She was reportedly found to have poor attention, was unable to repeat phrases, and was minimally able to follow commands. S. appeared to be responding to internally generated stimuli, saying things such as, “They are talking to my old mother. They are abusing me.” Her exam was non-focal and she was afebrile. Preliminary laboratory evaluation, including blood work and urinalysis, revealed mild dehydration with elevated bicarbonate and ketones, decreased thyroid stimulating hormone (TSH) and slightly elevated white blood cell count. The working differential diagnosis was delirium versus acute psychosis secondary to a primary psychiatric disorder. Continuous electroencephalogram (EEG) was ordered, and eventually neuroimaging; records indicated that there was less suspicion of encephalitis or a primary organic etiology, as there had been a past history of similar, less intense, and less prolonged episodes.
S. was interviewed by the psychiatry team in the emergency room with her mother initially present, during which she was more calm and lucid. Additional questioning revealed that S. had apparently overheard a conversation in which her mother spoke of increasing difficulty in caring for S. During the interview, S. repeatedly pointed to her mother and said she had been abused and was not her real mother. She reported that her mother was trying to poison her. She denied hearing voices and stated that she was talking to herself “to calm myself down.”
S. was admitted to the pediatrics unit where she was rehydrated and continued on her previous regimen of baclofen 5 mg three times a day (TID). She was started on quetiapine and lorazepam as needed by the psychiatry consultation service. Her urine and serum normalized, and the EEG and magnetic resonance imaging (MRI) were negative for any acute pathology. Additional laboratory studies including serum ceruloplasmin, B12, antinuclear antibody (ANA), and urine toxicology were normal. There was no lumbar puncture performed as it was not recommended by neurology. Endocrinology was consulted regarding mild hyperthyroidism, which they felt was unlikely to be contributing significantly to her acute presentation. S. remained paranoid and disorganized and was transferred to the inpatient adolescent psychiatric unit for continued observation and treatment.
Hospital Course
S. arrived on the unit agitated, shouting, and trying to throw herself out of her wheelchair and bed. She was put on constant observation for much of her course. She was given quetiapine, initially immediate release, in twice-daily (BID) dosing with which she was erratically compliant. Eventually, she was able to adhere to a regimen of extended release quetiapine before bedtime daily, titrated to a maximum dose of 900 mg. She had a minimal response even at the maximum dose. Benzodiazepines were rarely given in favor of quetiapine as needed.
Over several weeks, S. remained suspicious and paranoid, and at times was combative with staff. She appeared to be hearing voices and at times would respond in an angry manner. Her thought content involved delusions that her teachers and mother were persecuting and abusing her, both physically and emotionally. Meetings with her family and teachers seemed to discount her accusations and there was no evidence to suggest that her family and specialized school were anything but devoted, compassionate care-takers for S. There were no past traumas identified or suspected, as S. had been in round-the-clock care by family and trusted professionals for most of her life. School staff did mention that there were some changes recently in her class. While last year S. was “the star” and had a very supportive teacher, this year she was paired with more intellectually advanced youth, and her teacher was not as involved in giving her positive reinforcement as the teacher last year had been.
S. had an extended hospital course. At times she appeared calm, friendly, and well-organized, while at other times she appeared to be floridly psychotic and agitated. Her behavior fluctuated from day to day without any observable pattern or precipitants. S.'s sleep and appetite were adequate, although on a few occasions when she was acutely agitated, she stayed up all night, talking to herself, and disturbing the unit. By the next day she would sleep and appear to be calm. On one such evening, the resident on-call administered intramuscular haloperidol to which she had a good response and tolerated well with no adverse effects.
The team, including the neurology service, subsequently reconvened to review the case at length. It was felt that S. had had an adequate trial of quetiapine extended-release at sufficient dosage with minimal treatment response. The initial choice of quetiapine over a more potent dopamine-2 receptor (D2-R) antagonist such as risperidone was influenced heavily by a desire to minimize potential extrapyramidal side effects in light of S.'s spasticity secondary to CP. At this point the team decided that the risk of exacerbating S.'s spasticity was outweighed by the benefit that a more potent D2-R antagonist could give by alleviating her psychotic symptoms. The next step, if a trial of a second neuroleptic failed, would be to initiate a mood-stabilizer, such as valproic acid. The well-tolerated administration of haloperidol by the on-call resident gave more support to this strategy. In addition, the endocrinology service was consulted to evaluate management of catamenial (menstrual) psychosis, and they recommended keeping a log of symptoms and a trial of oral contraceptives, which was refused by the patient and her mother.
During the few days that the team was deciding on the next course of treatment, S. had been calmer and better organized. However, about one week prior to her menses, S. rapidly deteriorated. The decision was made to begin a rapid cross-titration of quetiapine for risperidone. S. complained of nausea and had a few episodes of vomiting during the first few days of the cross-taper, but even on a dose of 1.5 mg of risperidone, there was a solid improvement. S. became much less irritable, with apparent resolution of auditory hallucinations, and she was able to converse in a goal-directed manner, expressing insight into her recent symptoms. This continued at a dose of risperidone orally disintegrating tablet 1 mg BID and discharge planning was accelerated. S. maintained her improved status.
Past Psychiatric History
There was no previous psychiatric history. S. was evaluated by a school psychologist in the past around issues of frustration and self-esteem. There was no past cognitive testing available to ascertain her level of intellectual functioning.
Developmental History
Mother's pregnancy was complicated by premature rupture of membranes at 32 weeks. One week later S. was delivered, weighing 3 lbs. 1 oz. She was treated in the neonatal intensive care unit for prematurity and respiratory distress for 5 weeks. CP was diagnosed at 11 months following a head computed tomography (CT) scan showing the morphological signs of anoxic brain injury. Developmental milestones were globally delayed.
S. was referred for early intervention at around age one year. With regard to adaptive functioning, according to mother, S. is able to write, albeit with difficulty from contractures, do math, speak in sentences, and carry on conversations. She is reported to be knowledgeable about popular radio songs.
Educational History
S. has received special education services at a regular public school. Four years prior to admission, following some teasing episodes at her first school, she was referred to a specialized school for children with CP. She receives occupational, physical, and speech therapy at school. By all accounts she was doing well the school year prior to this episode, academically and socially.
Social History
S. lives with her biological mother, stepfather, and two half siblings under the age of 5. Parents are divorced, and biological father has been intermittently involved in her life.
S. has limited social relationships, mostly confined to school. She is reported to be up-to-date about hip-hop music and is interested in boys.
Family History
There is no known family psychiatric history of psychotic or affective illness, or developmental delays.
Medical History
S. was hypoxic at birth but never intubated. She reportedly received continuous positive airway pressure (CPAP) for one day. S. carries a diagnosis of CP with spastic quadriplegia. She has a past surgical history of hamstring lengthening, strabismus surgery, and dorsal rhizotomy.
She is followed at a neuromuscular clinic and has been taking baclofen for some time with no recent adjustments in her regimen. Her brain MRI with and without contrast showed mild hyperintense fluid attenuated inversion recovery (FLAIR) throughout the periventricular white matter. The lateral ventricles were dilated and dysmorphic. There was prominence of cerebral sulci bilaterally, involving the parietal and occipital, and to a lesser extent, frontal and temporal lobes.
Medication History
There was no previous history of psychotropic medication other than occasional clonazepam 0.125 mg as needed. S.'s current regimen is risperidone orally disintegrating tablet 1 mg BID and baclofen 5 mg TID.
Mental Status Examination
S. was an adolescent of average build, sitting in a wheelchair with a belt around her waist, with adequate grooming overall but unkempt dark, shoulder length hair. There were no dysmorphic features. No tics or psychomotor abnormalities were noted, but she remained seated and upper body movements were minimal. She did not appear to be in physical discomfort. She had fair eye contact, though at times her eyes wandered and she grinned inappropriately. Her speech was over-productive but not pressured. It was slightly slurred with normal rhythm and prosody. S. was loud and pleading at times. Her thought process was concrete; at times it was perseverative but was mostly goal-directed and logical. She derailed at times but could be redirected. She was well-related, comical, and affectionate, although dysphoric at times with staff. She described her mood as “upset.” Affect was childish, irritable, labile, and inappropriate. S.'s thought content was notable for delusions of persecution and misidentification, and ideas of reference. S. denied most mood and anxiety symptoms. She consistently denied auditory or visual hallucinations, though she appeared grossly internally preoccupied at times, having entire conversations with herself. Her reality-testing appeared impaired. She was not oriented to time but was oriented to person and place. Her insight and judgment were poor, and her impulse control was fair.
Brief Formulation
In summary, S. is a 17-year-old adolescent girl with a diagnosis of CP with spastic quadriplegia secondary to an anoxic brain injury at birth. She initially presented as floridly psychotic with new-onset symptoms, including disorganized speech and behavior, persecutory delusions, and assumed auditory hallucinations. Her history was notable for mood lability, bizarre behavior, and internal preoccupations in the past, reportedly brief, limited, and in possible temporal association with menses. Her admission was precipitated by a protracted and intense episode characterized by fluctuating symptoms and initial resistance to high doses of quetiapine. Several psychosocial stressors prior to the onset of illness included challenges to her self-esteem at school, both academically and socially, and perhaps anxiety regarding her family's continuing ability to take care of her.
Treatment during the hospitalization was notable for rather rapid response to risperidone, which was initially deferred in light of her neuromuscular condition. At the time of discharge, it was unclear whether her clinical picture represented the emergence of schizophrenia, continuation of an affective psychosis, a still undetected delirious process, though unlikely at this point considering the negative medical work-up, or the superimposition of a maladaptive reaction to adolescent stressors on underlying neurological and cognitive dysfunction.
Multi-Axial Diagnoses
Discussion
This case represents some of the diagnostic and treatment challenges that may arise when faced with the emergence of acute-onset psychotic symptoms in an adolescent with cerebral palsy. CP is an umbrella term describing nonprogressive brain lesions formed in early development that result in gross motor, postural, and often, cognitive impairment. One definition of CP is "a group of disorders of the development of movement and posture causing activity limitations that are attributed to nonprogressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, cognition, communication, perception, and/or behavior and/or a seizure disorder" (Bax et al. 2005). According to the Centers for Disease Control, in 2004 the average prevalence was 3.3 per 1,000 eight-year-old children (Centers for Disease Control and Prevention: Cerebral Palsy). Although CP is an organic brain disease in which a significant proportion of children have psychiatric co-morbid disorders, much more emphasis in the literature has been paid to the management of the physical rather than the psychological manifestations.
Children with CP are reported to have an increased rate of psychiatric disorders. Psychiatric consequences of childhood brain disorders may result from several underlying mechanisms, including characteristics of the brain lesion itself, associated intellectual impairment, co-morbid disorders, effects of impaired sensorimotor and speech/language, family parental psychopathology and functions, and environmental protective and risk factors (Masi et al. 2010). Rutter's classical 1970 epidemiological Isle of Wight study reported that about half of children with CP had psychiatric disorders (Rutter et al. 1970). Low intelligence quotient (IQ) and reading deficits increased the risk; hyperkinetic disorder was the most common psychiatric disorder noted. According to one more recent cross-sectional multi-center survey of 818 children between the ages of 8 and 12, about one-quarter exhibited significant psychological symptoms on the Strengths and Difficulties Questionnaire. Higher scores were predicted by moderate to severe intellectual impairment, no siblings, or disabled siblings, and severe physical pain (Parkes et al. 2008).
An important question is whether there is a characteristic presentation of psychiatric illlness, and specifically, mood and psychotic symptoms, in patients with CP. It is possible that there is an association between neuropathological changes, seen as an etiological factor in CP, and white matter changes in juvenile-onset bipolar disorder, as suggested by Craven et al. (2002).
There are few descriptions regarding the presentation and treatment of severe psychiatric disorders in this population. Foster et al. (2010) describe a 15-year-old girl with CP with an acute onset of dramatic mood and psychotic symptoms treated with a combination of antipsychotic and anticonvulsant medications. There are similarities between S. and this adolescent, in that they both experienced an acute onset of florid, fluctuating psychotic symptoms, with insomnia and agitation.
An additional question is whether a different or unique approach to pharmacological treatment of psychotic symptoms in adolescents with CP, compared to adolescents without CP, should be used. S. was treated with antipsychotic medications, known to cause extrapyramidal side effects (EPS), which could theoretically lead to greater motor impairment superimposed on already severe motor and postural disabilities. As there is little literature on pharmacological treatment of severe psychiatric disorders in this population, more investigation is needed regarding the safety and efficacy of psychotropic medications.
Another interesting issue is the apparent temporal association of S.'s mood and psychotic symptoms with menses. Although there have been descriptions of this phenomenon since the mid-nineteenth century, contemporary study is lacking. The DSM-IV-TR's premenstrual dysphoric disorder does not adequately capture the phenomenology of S's disorder. A definition of menstrual psychosis proposes acute onset of psychotic symptoms of brief duration with full recovery, with “a circa-menstrual periodicity in rhythm with the menstrual cycle” (Brockington 2011). Although there is no consensus regarding treatment, conventional psychotropic medication, as well as treatment with oral contraceptives, has been used (Brockington 2011). Of importance is the necessity for accurate dating. For S., it was recommended that mother keep a log of her symptoms to examine which phase of her cycle coincided with symptoms. Whether those in the CP population are more susceptible to catemenial mood changes and psychotic symptoms has not been investigated, though case reports of mentally retarded individuals with aggression and self-injurious behavior in temporal association with menses has been described (Colella et al. 1992; Taylor et al. 1993).
Finally, it is important to note that S.'s symptoms occurred in the context of psychosocial stress, including concerns about her family's ability to provide care, limited peer relationships, and low self-esteem. Individuals with CP have been reported to have issues with social and family adjustment, as well as low self-concept (Shields et al. 2006; Blum et al. 1991). S.'s cognitive delays, as well as physical discomfort associated with the quadriplegia may have also rendered her more prone to affective dysregulation and mood disturbances.
In conclusion, additional research on the prevalence, course, and phenomenology of psychiatric illness in youth with CP is necessary to enhance our understanding of risk and protective factors and to develop effective treatment strategies.
Disclosures
Dr. Grody has no conflicts of interest or financial ties to disclose. Dr. Coffey has received research support from Eli Lilly Pharmaceutical, NIMH, NINDS, Tourette Syndrome Association, Otsuka, Shire, Bristol-Myers Squibb, Pfizer, and Boehringer Ingelheim.
Footnotes
Acknowledgment
We would like to thank Resham Gellatly, Tejal Kaur, and Claire Jaffe for their assistance in review and preparation of the manuscript.