The Curse of the Dolphins: Cognitive Decline and Psychosis : Journal of Developmental & Behavioral Pediatrics (original) (raw)

Anne Tsai, MD

Microarray analysis revealed a 210-kb interstitial deletion in 14q13.1 which contains NPAS3. The NPAS3 gene encodes a neuronal transcription factor that is implicated in psychiatric disorders.1 In the mouse model, NPAS3 disruption leads to reduced expression of reelin. NPAS3 carries out diverse functions such as circadian oscillations, neurogenesis, toxin metabolism, hypoxia, and tracheal development.2 The mouse knockout model has behavioral and hippocampal neurogenesis defects. Human chromosomal translocation at this locus has been associated with schizophrenia.3 Reelin is reduced in patients with schizophrenia and psychotic bipolar disorder. In addition, a comprehensive metabolic laboratory evaluation was negative.

Arlene Hagen, MD

Accurate diagnosis of childhood schizophrenia is essential and must first exclude a medical illness such as seizure disorder. The differential diagnosis in this case included psychogenic nonepileptic seizures, which may occur in schizophrenia, bipolar disorder, attention-deficit hyperactivity disorder, posttraumatic stress disorder, and mood disorders with anxiety or panic.1 An accurate diagnosis is required to treat effectively and reduce unnecessary exposure to antiepileptic drugs. Therapy is aimed at the underlying psychiatric condition.

Childhood-onset schizophrenia (COS) is a rare, chronic mental illness with estimated prevalence of 1 in 10,000. Symptoms in common with the adult type of schizophrenia include hallucinations, delusions, flat affect, limited motivation, and anhedonia. COS and intellectual disability co-occur 3 times more frequently than would be expected by chance. Negative symptoms (problems with motivation, social withdrawal, diminished affective responsiveness, speech, and movement) are seen more frequently in children with intellectual disability.2 Isela had affective flattening and decreased self-care as well as positive symptoms of laughter, pacing, crying, and hand wringing.

Treatment of COS optimally involves early intervention with a multidisciplinary team including a psychiatrist, a psychologist, a pediatrician, a social worker, and psychiatric nurses. This approach positively impacts long-term outcome and prognosis.3 The primary form of treatment of COS is antipsychotic medication, individual therapy, family therapy, and social skills training. Individual therapy is focused on engagement and social relationships in school. The family therapy component focuses on improving communication skills, reducing anxiety and criticism, and supporting the family in coping with their child's mental illness.

Use of atypical antipsychotic medication for COS is beneficial, but has multiple potential side effects, including weight gain, diabetes, lipid derangement, elevated prolactin, and rarely, movement abnormalities.4 These medications are useful in conjunction with the early intervention, multidisciplinary team approach.

Joseph Pinter, MD

With Isela's precipitous behavioral decline, it was important to rule out metabolic and infectious causes as well as seizures, as described above. A routine electroencephalogram (EEG), with Isela awake, did not reveal any epileptiform abnormalities. Fourteen months after the first EEG and following trials of anticonvulsant medication, which resulted in no clinical improvement, an overnight 28-hour EEG revealed no asymmetries or epileptiform abnormalities and normal sleep architecture. Video recordings of Isela shuddering, jerking, staring, or laughing (each for a few seconds), were made without associated epileptiform activity. Although a normal EEG does not rule out the possibility of epilepsy or seizures, it is reassuring that the brief episodes of sleep-associated giggling or laughter did not have an associated ictal electrographic pattern.

If the spells represented complex partial seizures, it is likely (but not always the case) that the EEG would have revealed abnormalities. Given that the episodes and behavior problems did not resolve with anticonvulsant medication but improved with an atypical antipsychotic and there was no EEG abnormality, the likelihood of these episodes representing seizure activity is very low.

Pseudoseizures are nonepileptic events in which patients subconsciously manifest unusual behaviors, often as a result of psychological stress or secondary gain. Pseudoseizures may be convulsive in appearance and often are inducible. Many patients with actual epileptic seizures also have pseudoseizures at some point. Although a normal EEG and a lack of response to anticonvulsant medications could be consistent with pseudoseizures, this patient does not have prominent jerking or long-lasting staring spells suspicious for pseudoseizures.

Gelastic seizures are associated with a hypothalamic hamartoma (HH) associated with mirthless laughter, often noted to be machinelike or staccato without normal emotional content.1 HHs are rare tumors that, like other tumors in the sellar region, can also affect behavior and appetite. HH-related gelastic seizures are more common in young children. Some children also present with precocious puberty with or without gelastic seizures. Other seizure types are also commonly associated with HH, including complex partial and generalized seizures (including drop episodes with a generalized loss of muscle tone). Gelastic seizures can go unrecognized in infants and young children when laughing is perceived as innocent. HH is suspected when other seizure types emerge or precocious puberty, severe behavioral problems, and/or progressive cognitive deterioration develop.2 In some cases of HH, seizures may not be accompanied by epileptiform changes on EEG, most likely due to the deep position of the tumor. In other cases, both focal and generalized epileptiform discharges are seen. A high-resolution brain magnetic resonance imaging (MRI) including sagittal, coronal, and axial sequences may be needed to detect a small hypothalamic hamartoma. Resolution of the gelastic seizures and behavioral improvement have been reported after surgical removal of the HH tumor.3

Isela's brain MRI at initial presentation and second MRI 14 months later were normal without any evidence of a hypothalamic or pituitary mass.

Raegan Smith, PhD

Isela's parents continued to express alarm about her decline after successful treatment of her psychotic symptoms. They were upset and surprised when informed that their daughter would need long-term support and continued medical treatment with psychotropic medication. Isela's father spoke on behalf of both parents to express disappointment in her prognosis. Convinced that Isela's experience with the dolphins was the cause of her symptoms, her father expressed frustration that the perceived decline in his daughter's function was not being treated.

Cultural and psychosocial factors are significant in this case.1 Isela's parents are Mexican immigrants with limited education. Isela's father spoke English. The clinician should assess the father's understanding of the assessment and plan and encourage him to explain it to his wife. The services of an interpreter should be offered.

The parents' understanding of Isela's cognitive capacities should be explored in the context of the family's culture. Her parents' perception of diminished functioning may have also been related to Isela's intellectual ability. With the emergence of adolescence, cognitive and behavioral differences compared with peers may become even more evident. These developmental contrasts may be associated with perceptions of greater impairment over time.2 The parents' belief that the dolphin's experience is a significant source for her decline should be addressed in a sensitive manner. A culturally competent approach supports for the patient and family in a manner that balances the medical assessment with the relationship with Isela and her family.

It may have been helpful to inquire about the parents' beliefs about Isela's symptoms at an early stage in the diagnostic process. Allowing adequate time to clarify the parents' questions is critical in developing trust to ensure parents' understanding of the medical findings.

However, culturally dependent perceptions about illness may not be shared by a clinician and family who come from different cultural backgrounds. Research among Latino patients shows that “… when the patient and clinician's explanatory models do not match, the cultural and clinical realities of what is perceived to be wrong, what caused the problem, and what type of treatment is most appropriate may conflict and lead to … greater disbelief in the service provided, treatment dissatisfaction… and less than optimal outcomes.”3 A culturally competent approach would assess the parents' level of acculturation and determine the explanatory model about psychological disorders. The therapeutic goal is then to provide culturally sensitive education to reduce stigma and improve openness regarding mental health treatment.4

Randall Phelps, MD, PhD

This author is a developmental-behavioral pediatrician who submitted this case and solicited the commentaries of the contributors.

Isela developed a regression, broadly affecting function and adaptive skills, associated with apparent hallucinations and disruptions of affect and sleep. A detailed neurological evaluation ruled out a seizure disorder; pseudoseizures explained her periodic movements and change in affect. She had a preexisting intellectual disability, developed childhood schizophrenia at the onset of puberty, and was found to have a genetic abnormality associated with schizophrenia and consistent with her psychiatric presentation.

Martin T. Stein, MD

Dr. Phelps suggested this Challenging Case as an example of a pattern of unusual behaviors evaluated by an effective multidisciplinary team. The members of the team brought a biopsychosocial framework to the evaluation process. My only suggestion is that, if possible, a Latino clinician on the health care team early in the evaluation process may have addressed some of the critical cultural concerns that were discussed by Dr. Smith. If this is not possible, an alternative is an experienced translator who is available at the beginning of the evaluation.

Pachter has defined culturally sensitive pediatrics as “care (that) respects the beliefs, attitudes and cultural life-styles of patients. It acknowledges that concepts of health and illness are influenced by patients' ethnic values, religious beliefs, linguistic considerations and cultural orientation.” A culturally sensitive pediatrician seeks to understand the family's explanatory model for the presenting symptoms by asking questions such as “What would you call this problem? Why do you think your child has developed it? What do you think caused it? What do you think is happening inside the body?”1

REFERENCE

1. Pachter LM. Practicing culturally sensitive pediatrics. Comtemp Pediatr. 1997;14:139.

Keywords:

childhood schizophrenia; pseudoseizure; cultural competency