Mood and behavioral dysfunction with opsoclonus-myoclonus ataxia.

Opsoclonus-myoclonus ataxia syndrome is a paraneoplastic syndrome of cerebellar damage associated with neuroblastoma. The authors assessed psychiatric symptoms of opsoclonus-myoclonus ataxia syndrome in 17 children, who were 16 months to 12(1/2) years of age. Psychiatric symptoms examined included disruptive behavior, affective dysregulation, irritability, impulsivity, cognitive impairment, and poor attention.

Longitudinal neurodevelopmental evaluation of children with opsoclonus-ataxia.

OBJECTIVE: We previously reported on children with opsoclonus-ataxia and found pervasive neurodevelopmental deficits, years after onset, without a clear relationship to treatment modality or timing of treatment. A significant negative correlation of functional status with age at testing raised a question of whether opsoclonus-ataxia is a progressive encephalopathy. We attempted to answer this question with serial testing. In addition, we examined the relationship between clinical course and developmental outcome. METHODS: Thirteen of 17 children with opsoclonus-ataxia, all with neuroblastoma, who were previously reported were reevaluated a second time 2 to 4 years after the initial assessment. One subject who lived out of state was partially reevaluated and is included. Five new subjects (2 with neuroblastoma and 3 without) were also enrolled. Each was evaluated twice at a minimum interval of 1 year between sessions. Intercurrent medical course was recorded, emphasizing medication and relapse history. Cognitive, adaptive behavior, academic, speech and language, and motor abilities were assessed. RESULTS: For the group as a whole, overall standardized, age-adjusted cognitive scores improved. Generally, younger subjects' cognitive and adaptive behavior scores improved more than older subjects. Although all subjects had gains in speech, language, and motor function, some progressed at a slow pace, and in some instances, standard scores dropped. There was a striking influence of clinical course. Although initial presentation was severe and all subjects required high doses of corticosteroids or corticotropin, 5 had a monophasic course and were able to be weaned from treatment without relapses. Fourteen had multiple relapses over the years, generally with reduction of medication or intercurrent illnesses. Of the 5 children with monophasic course, 4 are currently functioning in the average range with a full-scale IQ of > or =90 and age-appropriate academic and adaptive skills. CONCLUSIONS: The results continue to raise concern that opsoclonus-ataxia is sometimes a progressive encephalopathy. A minority of children with opsoclonus-ataxia have a monophasic course. Despite initial severity of symptoms, these children may have a more benign prognosis. For the majority of children with opsoclonus-ataxia, the course includes multiple relapses and requires prolonged treatment. Developmental sequelae are significant in these children with chronic course.

A high predisposition to depression and anxiety in mothers and other matrilineal relatives of children with presumed maternally inherited mitochondrial disorders.

Although mothers of chronically ill children are generally prone to depression and anxiety, clinical observation suggests that these symptoms are relatively increased in mothers of children with maternally inherited mitochondrial disorders (MIMD). In this study, the Beck Depression Inventory II (BDI), the Beck Anxiety Inventory (BAI), and a non-standardized mental health questionnaire were administered to 15 mothers of children with MIMD and 17 mothers of children with autosomal recessive metabolic disorders (ARMD) followed in one clinic. One half of the children in both groups suffer from mental retardation and/or > or = 2 hospitalizations/year related to their genetic disorder, and were labeled as severely affected. BDI and BAI scores were similar between mothers of severely affected MIMD and ARMD children, but BDI and BAI scores were threefold higher in mothers of mildly affected MIMD versus ARMD children (P = 0.001 and P = 0.003, respectively). Any mental health condition was self-reported in 10/15 MIMD and 2/17 ARMD mothers (P = 0.002), while at least one mental health condition per family was reported to be present in a matrilineal first-degree relative of the mother in 8/15 MIMD versus 1/17 ARMD families (P = 0.004). Our data confirm that mental health conditions, particularly depression, are diagnosed at an increased frequency among matrilineal relatives likely sharing the same mitochondrial DNA (mtDNA) as the affected proband. While previous studies have demonstrated that mtDNA sequences can affect brain function, our data suggests that in addition mtDNA sequences can predispose individuals towards the development of some "mental health" disorders. Thus, "genome-wide" studies to screen for genes associated with depression and anxiety should not neglect the small, yet important, mitochondrial genome.

Impulsivity and verbal deficits associated with domestic violence.

While neurobiological factors are known to play a role in human aggression, relatively few studies have examined neuropsychological contributions to propensity for violence. We previously demonstrated cognitive deficits among men who committed domestic violence (batterers) compared to non-violent controls. Batterers had deficits in verbal ability, learning and executive problem-solving ability. These findings led us to examine whether executive control problems involving impulsivity contribute to problems with behavioral control among batterers, and to further examine their deficits in verbal functioning. Batterers (n = 41) enrolled in a domestic violence program were compared to 20 non-violent men of similar age, education, and socioeconomic background on neuropsychological tests of executive functioning, including impulsivity. Questionnaires and structured clinical interviews were used to assess emotional distress, aggression and self-reported impulsivity. Batterers showed greater impulsivity compared to non-batterers on several neuropsychological measures. Yet, the severity of these deficits was relatively mild and not evident in all batterers. Consistent with our previous findings, significant verbal deficits were again observed among the batterers. These findings suggest that while impulsivity may be a factor associated with domestic violence, it probably is not the sole determinant of the strong relationship between cognitive functioning and batterer status that we previously observed. Both verbal expressive deficits and behavioral impulsivity appear to be relevant variables in predisposing men to domestic violence.

Opsoclonus-ataxia caused by childhood neuroblastoma: developmental and neurologic sequelae.

OBJECTIVE: Opsoclonus-ataxia, also called "dancing eye syndrome," is a serious neurologic condition that is often a paraneoplastic manifestation of occult neuroblastoma in early childhood. Despite resection of tumor and immunosuppressive therapy, outcome generally includes significant developmental and behavioral sequelae. There is controversy about how treatment alters outcome. The goals of this study were to understand the ongoing neurologic and developmental deficits of children who are treated for opsoclonus-ataxia with associated neuroblastoma; to relate treatment history to outcome; and to quantify objectively the acute changes in motor function, speech, mood, and behavior related to intravenous immunoglobulin (IVIg) treatment. METHODS: Patients were children with opsoclonus-ataxia caused by neuroblastoma, regardless of interval since diagnosis. Records were reviewed, and children underwent comprehensive evaluations, including neurologic examination and tests of cognitive and adaptive function, speech and language, and fine and gross motor abilities. Psychiatric interview and questionnaires were used to assess current and previous behavior. In 6 children, a videotaped standardized examination of eye movements was performed. Additional examinations were performed immediately before and 2 to 3 days after treatment with IVIg in 5 children. RESULTS: Seventeen children, ages 1.75 to 12.62 years, were examined. All had a stage I or II neuroblastoma resected 3 months to 11 years previously. None received any other treatment for the tumor. All but 1 had received at least 1 year of either oral corticosteroids or corticotropin (ACTH); 12 had received 1 or more courses of IVIg, 2 g/kg. Three had received other immunosuppressive treatment, including cyclophosphamide. Cognitive development and adaptive behavior were delayed or abnormal in nearly all children. Expressive language was more impaired than receptive language. Speech was impaired, including both intelligibility and overall output. Fine and gross motor abilities were impaired. Increased age was strikingly associated with lower scores in all areas. Behavioral problems early in the course included severe irritability and inconsolability in all; later, oppositional behavior and sleep disorders were reported. Opsoclonus abated in all, but abnormalities in pursuit eye movements were found in all 6 children cooperative with standardized examination. Outcome did not differ in children who were treated with ACTH versus oral steroids. Three children who had received cyclophosphamide fared poorly. Immediate versus delayed treatment was not associated with better outcome. IVIg improved both gross and fine motor and speech function acutely, but we could not confirm long-term benefit of IVIg. Total number of courses of IVIg was not associated with outcome. CONCLUSIONS: Opsoclonus-ataxia caused by neuroblastoma causes substantial developmental sequelae that are not adequately prevented by current treatment. The increased deficits in older children raise concern that this represents a progressive encephalopathy rather than a time-limited single insult. Although the study is cross-sectional and neither randomized nor blinded, we were unable to confirm a purported advantage of either ACTH over corticosteroids or of cyclophosphamide. A randomized study is needed but is difficult for this rare condition.