Ultrasound and magnetic resonance imaging for group stratification and treatment monitoring in the transgenic adenocarcinoma of the mouse prostate model.

BACKGROUND: The transgenic adenocarcinoma of the mouse prostate (TRAMP) is a widely used genetically engineered spontaneous prostate cancer model. However, both the degree of malignancy and time of cancer onset vary. While most mice display slowly progressing cancer, a subgroup develops fast-growing poorly differentiated (PD) tumors, making the model challenging to use. We investigated the feasibility of using ultrasound (US) imaging to screen for PD tumors and compared the performances of US and magnetic resonance imaging (MRI) in providing reliable measurements of disease burden. METHODS: TRAMP mice (n = 74) were screened for PD tumors with US imaging and findings verified with MRI, or in two cases with gross pathology. PD tumor volume was estimated with US and MR imaging and the methods compared (n = 11). For non-PD mice, prostate volume was used as a marker for disease burden and estimated with US imaging, MRI, and histology (n = 11). The agreement between the measurements obtained by the various methods and the intraobserver variability (IOV) was assessed using Bland-Altman analysis. RESULTS: US screening showed 81% sensitivity, 91% specificity, 72% positive predictive value, and 91% negative predictive value. The smallest tumor detected by US screening was 14 mm3 and had a maximum diameter of 2.6 mm. MRI had the lowest IOV for both PD tumor and prostate volume estimation. US IOV was almost as low as MRI for PD tumor volumes but was considerably higher for prostate volumes. CONCLUSIONS: US imaging was found to be a good screening method for detecting PD tumors and estimating tumor volume in the TRAMP model. MRI had better repeatability than US, especially when estimating prostate volumes.

Ultrasound-Mediated Delivery of Chemotherapy into the Transgenic Adenocarcinoma of the Mouse Prostate Model.

Ultrasound (US) in combination with microbubbles (MB) has had promising results in improving delivery of chemotherapeutic agents. However, most studies are done in immunodeficient mice with xenografted tumors. We used two phenotypes of the spontaneous transgenic adenocarcinoma of the mouse prostate (TRAMP) model to evaluate if US + MB could enhance the therapeutic efficacy of cabazitaxel (Cab). Cab was either injected intravenously as free drug or encapsulated into nanoparticles. In both cases, Cab transiently reduced tumor and prostate volume in the TRAMP model. No additional therapeutic efficacy was observed combining Cab with US + MB, except for one tumor. Additionally, histology grading and immunostaining of Ki67 did not reveal differences between treatment groups. Mass spectrometry revealed that nanoparticle encapsulation of Cab increased the circulation time and enhanced the accumulation in liver and spleen compared with free Cab. The therapeutic results in this spontaneous, clinically relevant tumor model differ from the improved therapeutic response observed in xenografts combining US + MB and chemotherapy.

Nature of anxiety comorbid with attention deficit hyperactivity disorder in children from a pediatric primary care setting.

The clinical characteristics of children with comorbid anxiety and attention deficit hyperactivity disorder (ADHD were examined. A sample of children from a pediatric primary care practice was assessed for anxiety disorders and ADHD. We defined four groups of children: (1) anxiety disorders only with no ADHD (n=54); (2) ADHD-only with no anxiety disorder (n=15); (3) neither ADHD nor an anxiety disorder (n=107); and (4) comorbid ADHD and anxiety disorder (n=14). Approximately 50% of children with ADHD had a comorbid anxiety disorder, and approximately 20% of children with an anxiety disorder had comorbid ADHD. The presence of comorbid ADHD and anxiety was associated with more attentional problems, school fears, and mood disorders and lower levels of social competence compared to children who had either ADHD-only or anxiety-only. Children with comorbid anxiety disorders and ADHD have more severe symptoms and are more impaired than children with either condition alone. Interventions need to be tailored to address the complexity of these comorbid conditions and their associated sequelae.

Barking vocalizations and shaking movements in a 13-year old girl.

CASE: Erica is a 13-year old female who was hospitalized for a 4-week history of "barking" noises and 2 weeks of generalized shaking episodes. Four weeks prior to admission, she had a viral upper respiratory infection (URI) with cough which was treated with over-the-counter cough syrup. After resolution of the URI, she developed a persistent cough that turned into a "bark"-like vocalization. Both the mother and patient demonstrated the bark as an "arf" sound like that of a small dog at times, a large dog at others. These vocalizations were unrelenting, occurring 3-10 times per minute only while awake. They were not precipitated by any known factors nor were there alleviating factors. She could not voluntarily suppress the sound. In addition to the vocalizations, episodes of generalized shaking of the extremities began 2 weeks prior to admission. According to Erica's mother, each episode lasted about 10-60 seconds and occurred 30-40 times a day only when she was awake. These episodes were not rhythmic or symmetric, and they were not associated with bowel or bladder incontinence. There was no alteration of consciousness following the episodes. Erica denied any recollection of the barking or shaking.The medical evaluation did not reveal an etiology. It included a complete physical examination, a neurological examination, biochemical laboratory studies, and a negative video EEG study that captured 10 episodes of shaking. Child psychiatry was consulted. Erica was a pleasant, quiet female with slightly constricted affect and a normal speech pattern. She reported that she was a straight-A honors student who had difficulty trusting others; she said that she had no friends, only "associates." She said that she had periods of feeling "sad" and crying easily, but could not identify any recent stressful event. Episodes of barking and shaking diminished during the hospitalization. Erica was discharged home with outpatient psychiatric follow-up.

When disclosing a serious diagnosis to a minor conflicts with family values.

An 11-year old Asian-Indian boy was recently discovered to have acute myelogenous leukemia. The pediatric hematologist-oncologist arranged a meeting to inform the parents about the diagnosis, prognosis and treatment. The physician planned to include the child in this process. However, the child's father, a computer programmer, made a request that his son should not be informed about the diagnosis of leukemia. The father asked that his son should be told that he has a severe infection and will require intensive treatment. The oncologist then informed the father that, as a physician, she has the responsibility to truthfully disclose the diagnosis to a patient, and she insisted on informing the child about the leukemia in an open and truthful manner.

When a Child Unexpectedly Draws a Violent Scene.

CASE: Carter is a 12-year-old boy who has been seeing a developmental-behavioral pediatrician since the age of 7 years for problems with behavioral regulation. Around that time, he began to receive special education services after an educational assessment of autism. He has average intellectual abilities, with below-average semantic-pragmatic speech (e.g., conversations are one-sided). His medical diagnoses included attention-deficit hyperactivity disorder (ADHD), combined presentation, and generalized anxiety disorder. He has never met the DSM criteria for autistic spectrum disorder (ASD) because although he has atypical sensory behaviors (e.g., preoccupied with sniffing objects), he has otherwise lacked restricted, repetitive behaviors. Other medical problems include obesity.His functional impairments associated with impulsivity, inattention, and anxiety improved with combined pharmacotherapy (a long-acting stimulant and a selective serotonin reuptake inhibitor [SSRI], on which he remains) and cognitive-behavioral therapy (CBT). After starting sixth grade, his Individualized Educational Plan (IEP) was modified to address his social impairments, with a self-contained classroom without windows. Soon thereafter, he began to talk about "hating myself" and developed mild-to-moderate depression, which improved after several weeks of a higher dose of SSRI and more frequent visits with his therapist.Several weeks after starting seventh grade, the teacher sent an email to Carter's parents, which they forwarded to his developmental-behavioral pediatrician: "Carter drew a picture of himself shooting and stabbing a student he was mad at today (). He was very upset when I told him I was going to tell you. We haven't processed it through yet but I think a conversation at home about appropriate drawings and using other ways to calm down would help this not happen again."

Disruptive Behavior, Global Developmental Delay, and Obesity in a 5-Year-Old Boy with a Chromosome Microduplication.

CASE: Ryan is a 5-year-old boy who was seen in a Developmental Behavioral Pediatrics clinic for disruptive behavior and developmental delay. His medical history was notable for a tethered spinal cord repaired at age 4 months, alternating exotropia with multiple surgeries, and obesity (body mass index at 99%). Ryan's development was globally delayed. He sat at age 10 months and walked at 24 months. An Autism Diagnostic Observation Schedule-Toddler module (ADOS-T) was completed at age 19 months and demonstrated little-to-no concern for autism spectrum disorder.Ryan's parents described behavioral challenges including hyperactivity, impulsivity, aggression toward him self and others, severe tantrums, a short attention span, and difficulty sleeping. They also endorsed repetitive behaviors including head rocking, walking in circles, and perseverative speech. Expressive language was significantly limited. There was no family history of autism or intellectual disability.Ryan's physical examination was notable for alternating exotropia, hypertelorism, upslanting palpebral fissures, and obesity. His speech was limited to 1-word utterances. Neurological and general examinations were normal.He was referred for repeat psychological testing at age 5 years. The ADOS-2 (Module 2) was consistent with a classification of autism with a high level of autism-related symptoms. A fragile X test was negative, and microarray demonstrated a microduplication in the region of 2p25.3 including the myelin transcription factor 1-like gene.

Episodic hypersomnia and unusual behaviors in a 14-year old adolescent.

CASE: John, a 14-year old white male of European Jewish descent without a prior history of medical or psychiatric problems, presented following several days of increased need for sleep (16-20 hours per day), disorientation, difficulty maintaining attention and concentration, bizarre behaviors. He was sexually inappropriate toward his mother, sister, and housekeeper, masturbated in public, and sang nonsense lyrics. In addition, he had brief periods of agitation, paranoia (including fear that he was being followed and that he would be hurt by the physicians), and periods of distraction by auditory and visual hallucinations. His appetite increased significantly during this time. One week prior to the onset of these symptoms, he traveled to the Midwest where he experienced several days of nausea, vomiting, and diarrhea.John's physical and neurological examinations were normal except for the behaviors noted above. A medical evaluation revealed a normal brain computerized tomogram (CT) and magnetic resonance imaging (MRI). Urine toxicology screen, a comprehensive metabolic blood panel, and a complete blood count were normal. A lumbar puncture demonstrated a slightly elevated opening pressure (24 centimeters); the cerebrospinal fluid examination was unremarkable for cells, protein and glucose. Following the lumbar puncture, for which he had received midazolam, he had a brief, 30-45 minute episode of lucidity in which he was able to describe feeling like he was "in a fog."John was transferred to a psychiatric hospital where he recovered over several days and was discharged home. After three weeks of complete recovery, he acutely developed profound fatigue and the previously seen bizarre behaviors returned and persisted for 2 weeks. Following a 2-week period without symptoms, a similar behavior pattern recurred for the third time. The third episode differed from the first two in that he initially developed mental status changes and then developed symptoms of hypersomnolence. John has now been completely recovered from the third two week episode for one week and is taking summer school classes and enjoying socializing with his friends.

Giving bad news: a 13-year old with acute psychotic symptoms and catatonia.

CASE: Scott, a 13-year 7-month old white male with no prior psychiatric history, presented to the emergency department after three days of decreased attention span and increased distractibility. An initial examination revealed that he was internally preoccupied (focused on responding to auditory hallucinations), displayed thought blocking (sudden interruption in the flow of his thoughts that prevented him from completing an idea), and he had periodic vague suicidal ideation due to intense guilt. He noted hearing two to three voices accusing him of being rude during an incident with a peer at school. He could not accept reassurance from his mother and grandparents that this incident had not actually occurred. Scott found evidence of his wrongdoing by misinterpreting words on signs and medical equipment that he felt indicated that others also knew of his malicious actions. A recent stressor included the conclusion of his active football season a day prior to the onset of his symptoms. Scott and his family denied a history of prodromal symptoms, mental or medical illnesses, including head injury. After a physical/neurological examination, a negative urine drug screen, and a normal complete blood count and metabolic panel, Scott was transferred to a psychiatric hospital. Scott returned to the emergency department two days later with worsening psychotic symptoms despite a trial of olanzapine. He had deteriorated dramatically from his initial presentation. He was now rigid, unable to speak, move his body, follow directions, eat, drink, or provide any additional history. After being admitted to the pediatrics floor an extensive medical workup was completed that included neurology and infectious disease consults, brain magnetic resonance imaging and angiography studies, a 24-hour electroencephalogram, lumbar puncture, urinalysis, complete blood count, comprehensive metabolic panel, ceruloplasm, anti-nuclear antibody, anti-DNAase, erythrocyte sedimentation rate, heavy metal screen, ammonia, rapid plasma reagin (RPR), and human immunodeficiency virus. All laboratory studies were normal.

Epilepsy surgery in an 8-year-old boy with intractable seizures.

CASE: Mark is an 8-year-old boy with a history of intractable epilepsy. Mark's seizures started when he was five years old, lasting less than a minute, with 7-10 episodes occurring in succession. Daytime seizures were described by his parents a "staring events where he does not respond, he will pick at clothes and speak gibberish." He was often disorientated for the remainder of the day. Nighttime seizures were described as "sitting up straight in bed, staring at the ceiling, and being unresponsive." An increase in his seizure frequency after multiple anticonvulsant medications prompted a surgical evaluation. A magnetic resonance (MR) brain scan indicated mild encephalomacia in the left hemisphere. A video electroencephalogram (EEG) demonstrated that the seizures initiated from the left hemisphere in association with multiple subclinical seizures. A PET scan showed decreased uptake in the left frontal lobe compared to the right. At 7 years of age Mark underwent a left frontal temporal-parietal resection. He had a post-surgical infection, but no other medical sequelae. After surgery, there was a significant decrease in seizures with only one seizure in the 2 month post operative period. Mark had neuropsychological testing prior to and following surgery. Pre-surgical results indicated that his IQ was within the low-average range. Visual-perceptual abilities, motor tasks and attention domains indicated difficulties. Post-surgical neuropsychological evaluation revealed a positive outcome. IQ remained in the low average range and there was a mild improvement in visual-perceptual/visual-constructional areas. Academic skills were unchanged with the exception of a slight decline in reading ability. Attention scores improved although redirection was required to sustain his attention during tasks. An increase in non-compliant behavior and emotional liability was noted by his parents.At the time of referral, when Mark was 8-years 3-months old, parental concerns included inattention, anger and emotional lability. The referral question posed was: "Does Mark's inattention represent an attention deficit/hyperactivity disorder, anxiety, or other psychological problems and what is the relationship of his current behaviors to his epilepsy?"

Significant Sleep Dysregulation in a Toddler With Developmental Delay.

CASE: Derrick's parents made an appointment with a new pediatrician for a second opinion about disordered sleep. Now 22-months old, he was evaluated at 18 months of age for developmental delay when he was found to have "a regulatory disorder associated with delays in language and motor development, hypotonia and significant sleep problems." The parents are now most concerned about his sleeping pattern. Prolonged sleep onset and frequent night awaking occur each night since 6-months of age. These problems are more severe in the past few months when he awakes screaming and cannot be settled. The awakening episodes occur 2 to 4 times each night when "he screams and thrashes his body for up to an hour." Daytime tantrums increased. After the parents read a book about sleep in young children, they provided a calm atmosphere at bedtime including a dark room and singing a quiet lullaby. When these changes did not alter sleep, they purchased a vibrating mattress which was also unsuccessful.Derrick was born full term after an uncomplicated prenatal and perinatal course. He sat at 10 months, crawled at 12 months, and walked at 18 months. He currently drinks from a sippy cup and he can use a utensil to eat. He has few words saying only "no" and "mama" in the past month. Imitation of some words occurred recently. He has responded to simple directions in the past 2 months. Derrick passed the newborn audiology screen. He does not have difficulty swallowing and he does not drool. He plays with many different toys and he plays in parallel with his older brother who also experienced delays in motor and language development. His brother is now doing very well in school. There is no family history of cognitive delay, seizure disorder, cerebral palsy, early developmental delay (other than the brother) or a significant sleep problem. PHYSICAL EXAMINATION:: head circumference, length and weight (75th percentile). He had mild generalized hypotonia, mild weakness, 2+ symmetrical deep tendon reflexes, and absence of ankle clonus. His gait was slightly wide based, steady, and without a limp. Neither ataxia nor drooling was observed. He was easily engaged in play with the examiner without evidence of irritability. The remainder of the examination was normal.

Auditory Processing Disorder: What Does It Mean and What Can Be Done?

CASE: Julian, an 11-year-old boy in the sixth grade with a compliant disposition and a positive attitude, has had a significant decline in his academic performance over the last 2 years. He spends much of his time in the nurse's office with headaches and fatigue. He reports that he cannot concentrate or follow along in class. Vision and hearing screenings were normal.Julian's teachers report that although he has no behavior problem, he is inattentive and does not put forth the effort she feels he is capable of giving. He does not seem to be listening, and he is distracted by everyone around him. He often claims that he did not hear or understand the things that teachers explained several times. When teachers talk to him directly, he starts an assignment and usually finishes his work on time. Teachers observe that he has "attention-deficit hyperactive disorder (ADHD) like tendencies." A recent psychoeducational evaluation qualified Julian for special education services under specific learning disability in the area of auditory processing. An individual education plan will be developed within the next 2 weeks.Key indicators used to make this determination included the following: average standard scores on nonverbal tests of cognitive development, a below-average score in overall auditory processing (with particularly low scores in auditory reasoning and auditory memory), average scores in the areas of general memory and attention/concentration, and below-average composite scores in reading and written expression.Following a review of the assessment report, Julian's parents remain concerned about the possibility of ADHD. Prior to the special education assessment, the school provided the Vanderbilt Assessment Scales for Julian's parents to share with his doctors; it revealed elevated scores in ADHD symptoms (predominantly inattentive subtype). Julian's parents would like to learn about options for treatment that might improve his attention.

An 8-Year-Old Boy With Treatment-Resistant Encopresis.

CASE: Paul is an 8-year-old boy with a long-standing history of encopresis and enuresis. Potty training was initiated when he was 2 years old. At this time, his mother was absent from the home for 6 weeks when she cared for her ill father in a different city. The process of teaching Paul to use the bathroom was described as "inconsistent" due to multiple caretakers.Paul never successfully mastered bowel and bladder control. He continues to wet and soil his clothes on a daily basis at home and school. According to his parents, he does not accept responsibility and comments about his soiling such as, "I didn't do it; someone else must have put it there." One of Paul's teachers commented that she could tell at the beginning of the school day whether he would maintain bowel and bladder control. If he was "agitated and talkative" in the early morning, he would often soil that day.He had a pediatric gastroenterological evaluation at the age of 5 years when he was having daily episodes of stool soiling. Physical examination revealed normal anal tone, normal placement of the anus, and moderate stool in the rectal vault. An abdominal radiograph revealed moderate stool throughout the colon. He was treated with Miralax and instructed to sit on the toilet twice daily. Paul did not respond to these interventions and was diagnosed with "overflow incontinence secondary to stool withholding." When he was taking Miralax, he had a normal barium enema radiograph. He was admitted to the hospital for a cleanout with a polyethylene glycol/electrolyte solution.Although abdominal radiographs demonstrated absence of colonic stool for the following 5 months, he continued to soil his clothing. Play therapy and biofeedback did not change the chronic soiling and wetting pattern. An evaluation at the Continence Clinic resulted in a rigorous program including stooling after each meal, wearing a vibrating watch reminding him to void every 2 hours, drinking 60 ounces of water per day, tracking elimination patterns on a calendar, and a daily laxative (polyethylene glycol). A neuropsychological evaluation revealed a superior aptitude associated with unresolved early childhood issues of self-control, self-care, and frustration tolerance. Family therapy was initiated. However, daily fecal soiling and wetting persisted.Paul was born full-term without prenatal or perinatal complications. He was breast fed for 1 year and described as an easy baby. He achieved motor, social, and language milestone on time. Paul had difficulty with separation and aggression in preschool (e.g., biting). In school, teachers report inattention, fidgetiness, and difficulty following directions. He has been obese since age 3 years; his current body mass index is 29.

Parental Influence on a Child's Autistic Traits.

CASE: Robbie is a 4-year-old boy whose parents are concerned about his speech, social skills, and repetitive behaviors. He has poor articulation; at time, he is difficult to understand. On the other hand, he has a fair vocabulary, and he has good intent to communicate. He is generally able to communicate his needs and wants. He likes to tell his parents about his day.When he begins the day at preschool, Robbie initially stands by himself and watches. He slowly warms up and eventually participates in activities. He engages in parallel play or follows other children. He knows names of children at preschool, and he is well liked. He is affectionate with his parents.When Robbie is excited, he wiggles his fingers, flaps his arms, and grimaces. He can be quite rigid; for example, he gets very distressed when his mother sets his cup down on his right side instead of his left. However, in general, Robbie has a sunny personality. He likes to watch children's television shows. He pretends plays with action figures. Robbie is an only child who lives with both parents. His mother works full-time, and his father is in home with Robbie during the day.When examined in the office, Robbie had a bright affect, good eye contact, and social referencing. He demonstrated good communicative intent, but poor articulation and some jargoning. He frequently wiggled his fingers and flapped his hands with excitement. Robbie had a borderline score on the Autism Diagnostic Observation Schedule.During the visit, the pediatrician noted that Robbie's father was rather quiet and rarely responded to questions. When he did respond, he had a monotone quality to his voice. He maintained either a flat or nervous affect throughout the visit. He made limited eye contact, and occasionally he stared excessively.

Weeding Out the Justification for Marijuana Treatment in Patients with Developmental and Behavioral Conditions.

CASE: Alex is a 13-year-old adolescent with high-functioning autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD)-combined type, anxiety, and depression. He has been resistant to engaging in therapy and treatment with various medications has been unsuccessful. Alex's parents are concerned about his anxiety, isolation, oppositional behaviors, academic underachievement, truancy, and substance use. A recent altercation with his stepfather led to a police intervention and a brief removal of Alex from the home. Alex previously used alcohol and other drugs; at present, he reports that his current drug use consists of frequently smoking pot. Alex states that he uses marijuana to relieve his anxiety and does not understand why this is problematic as marijuana is now legal in his state.Kevin is a 24-year-old adult man with diagnoses of autism spectrum disorder, mild intellectual disability, and schizoaffective disorder. He has a long history of challenging and problematic behaviors including aggression toward self and others, property destruction, inappropriate sexual behaviors, elopement, emotional outbursts, anxiety, and suicidal ideation. Past diagnoses include bipolar affective disorder, depression, and intermittent explosive disorder. Kevin is notably obese and somnolent. His current medications include 8 psychotropic medications, 3 antiallergy medications, levothyroxine, and a fish oil supplement. His father reports that medications have gradually been added and dosages increased over time. Two weeks ago, his new psychiatrist initiated a trial of medical marijuana. His father hopes that the marijuana will allow Kevin's other medications to be decreased or discontinued.Linda is an 11-year-old girl with high-functioning autism spectrum disorder, anxiety, and ADHD-inattentive subtype. Anxiety has been her most impairing condition, and Linda has been responding well to a treatment with cognitive behavioral therapy and a selective serotonin reuptake inhibitor. She is also working with her therapist on strategies to address her symptoms of ADHD. Linda has had no side effects from her medication and she and her family have been pleased with her progress. At a follow-up appointment, her mother brings an article from the lay press authored by a parent who claims that marijuana "saved" her autistic son. Linda's mother asks if marijuana should be considered for her daughter.

An 8-year-old Biological Female Who Identifies Herself as a Boy: Perspectives in Primary Care and from a Parent.

CASE: An 8-year 8-month-old biological female who self-identifies as a boy, Ricardo is brought by his mother for a well-child check to his new pediatrician. Ricardo and his mother report that he is doing well, but have concerns about the upcoming changes associated with puberty. Ricardo states that he is particularly afraid of developing breasts. His mother asks about obtaining a referral to a specialist who can provide "hormone therapy" to delay puberty.Ricardo was adopted from Costa Rica at the age of 2 as a healthy girl named "Angela." From the age of 3, he displayed clear preference for male gender-associated clothes, toys, and games. At age 5, his mother sought care for hyperactivity and sleep problems. He was diagnosed with attention-deficit hyperactivity disorder and sleep onset disorder at age 6, and his symptoms have been well controlled with Adderall and melatonin.Ricardo lives with his parents who are accepting and supportive of his gender preference. He sees a therapist who has experience with gender dysphoria. For the past years, he has attended school as male, with the confidential support of administrators at his elementary school.

A 9-Year-Old Girl With Persistent Obsessive and Compulsive Behaviors in a Primary Care Pediatric Practice.

CASE: Chloe is a 9-year-old gal whose mother made an initial visit to a new pediatrician for concerns about her behavior. Chloe is apprehensive about the visit and frequently hides behind her mother.Her parents first noticed Chloe becoming angry and more emotional 3 years ago, which her parents did not initially understand. However, over the past year, she has started to have more worries and unusual behavior.Chloe and her mother report that when she walks through doorways, she will almost always go back and walks through again. At home, she will walk through doorways multiple times and at school, she will pretend she forgot something so her friends do not notice. She often will not walk downstairs and occasionally her mother has to carry her. Clothes are problematic for Chloe. If her father touches something of a specific color and then touches Chloe, she will have to change her clothes or take a shower. Sometimes, she will never be able to wear those clothes again. She had a recent episode where she could not stop tapping a red paper, because if she stopped, she said it would burst into flame. During the 2 weeks before the pediatric visit, symptoms increased to the point that she is now refusing to go to school. When she stays home, she lays in 1 place all day.Chloe is a fourth grade student. The family does not report academic concerns. She has friends. She denies any appetite or sleep problems. She endorses periods of sadness, lack of energy, and decreased interest in social activities, mostly because she worries and is embarrassed. She kept her behaviors hidden from her 5 siblings for the past year, and she talked only to her mother about them. She is worried her friends might discover her behaviors.The family history is notable for multiple paternal family members with anxiety and bipolar disorder and depression on mother's side. A few months ago, Chloe's family adopted a 7-year-old child with special needs from China.Her growth, vital signs, and physical examination are unremarkable. Her mother filled out the Short Mood and Feelings Questionnaire and the Screen for Child Anxiety-Related Emotional Disorders, which both had elevated scores.

Sudden Onset of Refusal to Eat on Waking After a Nightmare in a 6-Year-Old Girl.

CASE: Bridgette is a 6-year-old girl, who presented with sudden onset of refusal to eat or drink. The only precipitating event was a nightmare the previous night. She described a dream in which her mother and maternal aunt, dressed as witches, and father and maternal uncle, appearing as bats, wanted to kill her by making her eat and drink from a cauldron. Bridgette stated, "I can't eat anymore, I'm afraid of dying." Bridgette's eating pattern and behavior were described as previously normal. Motor, social, and language milestones were also normal. Her parents reported that she occasionally refused nonpreferred foods, and they believed that her food intake had decreased at age 4 years. She was a full-term infant without perinatal problems and breast fed until 8 months. Her medical history was significant for strabismus surgery, before 6 months. Her mental health history revealed mildly depressed mood and irritability related to teasing at school after her strabismus surgery. Her parents described her as "always looking for attention." Her teachers reported that she had normal intelligenceand described her behavior as shy, slightly withdrawn, and distrustful. Social history revealed an only child of married parents without marital or work-related problems. Bridgette went to her maternal grandmother's home after school and during school holidays.Her parents pleaded with her to eat, but she refused. She was evaluated at urgent care where her physical examination was described as normal. Her body mass index was above the 97th percentile (3 SD above the mean). The parents were described as fearful and despairing. Laboratory tests included a complete blood count with differential, an electroencephalogram, and a computed tomography scan, all of which were normal. Intravenous fluids were administered on the day of presentation and the following day. She continued to refuse to eat or drink, and after 2 days, she was hospitalized for nasogastric tube feeding.

Inattentive Attention-Deficit/Hyperactivity Disorder, Stimulant Medication, and Weight Loss in a 15-Year-Old Girl: Are We Enabling the Development of an Eating Disorder?

CASE: Nicole is a 15-year-old girl presenting to the Developmental Behavioral Pediatrics Clinic with symptoms of the inattentive type of Attention-Deficit/Hyperactivity Disorder (ADHD) and declining school performance over the last year. She expressed frustration over her inability to concentrate on schoolwork. Assuming that her poor grades were secondary to lack of effort, her parents withdrew privileges. Nicole became increasingly depressed. She stopped participating in activities, she previously enjoyed, and her parents reported that she stopped singing in the shower. After talking to a cousin with ADHD, Nicole concluded that she had ADHD as well. She asked her parents to arrange for an evaluation.Nicole met DSM-5 criteria for the diagnosis of inattentive ADHD and was started on a stimulant medication (mixed amphetamine salts). She had symptoms of a coexisting depression, although she did not meet criteria for diagnosis of a depressive disorder. At a 3-week follow-up visit, she showed improvement in targeted ADHD symptoms; homework was now easier and her grades improved. At a 2-month follow-up, Nicole's weight dropped from 53 kg (47th percentile) prestimulant treatment to 49 kg (31st percentile). She reported appetite suppression after taking the stimulant but did not feel that her eating habits had changed significantly. Her father reported that she had a preference for junk food and snacks. Nicole did not enjoy exercising and did not participate in extracurricular sports.She weighed herself several times a day, as she was worried about losing too much weight. Nicole's mood continued to be low, despite the fact that her grades improved, and her parents were more understanding of her challenges. She was otherwise healthy and reported regular menstrual cycles. Nicole requested an increase in the dose of stimulant medication for greater improvement in concentration during homework and in school.Her pediatric clinician was concerned about the possibility of an eating disorder in addition to depression. She asked herself, "Are we treating inattentive ADHD effectively or are we enabling an eating disorder?"