Cognitive functioning in Lesch-Nyhan syndrome: a 4-year follow-up study.

Lesch-Nyhan syndrome (LNS) is a rare disorder of metabolism caused by a defective gene on the X chromosome. It is typically characterized by choreoathetosis, hypertonia, hyperreflexia, and self-mutilation. The present study is a 4-year follow-up investigation of the cognitive status of six subjects with a mean age of 17 years 10 months (range 14 years 9 months to 23 years). The Stanford-Binet Intelligence Scale: IV was used. Each of the four domains assessed by this battery (verbal reasoning, abstract/visual reasoning, quantitative, and short-term memory) was compared with previous findings of the same subjects at their initial test and 2-year follow up; the aim being to gain further insight into the clinical course of LNS over time. The results suggest that while the subjects generally continued to acquire new information and skills over time, their standardized scores declined, indicating that a plateau was reached in their skill levels relative to their peers, as also seen in other developmental disabilities. Deficits were noted in working memory, particularly on tasks that involve considering multiple features simultaneously.

Cognitive functioning in Lesch-Nyhan syndrome.

The present study represents the first effort to assess systematically the cognitive functioning of a population of individuals with Lesch-Nyhan syndrome using standardized psychometric instruments. Seven residents from a special hospital setting participated. They ranged in age from 10 years 1 month to 22 years 3 months (mean 13 years 7 months). Using the Stanford-Binet Intelligence Scale: IV, scores in each of the four domains assessed by this battery (Verbal Reasoning, Abstract/Visual Reasoning, Quantitative and Short-Term Memory), as well as the general composite score, ranged from moderately mentally retarded to low average. Areas of weakness included attention, the manipulation of complex visual images, the comprehension of complex or lengthy speech, mathematical ability, and multi-step reasoning.

Frequency of cocaine and phencyclidine detection at a large urban public teaching hospital.

To assess the value of the current NIDA cutoff concentrations for screening assays that detect urinary cocaine metabolites and phencyclidine (PCP), we collected data on concentrations of these drugs in newborns and patients admitted to the Los Angeles County + University of Southern California Medical Center from July 1, 1991, to December 31, 1991. Less than 2% of the patients were positive for PCP. However, 16.5% of the newborns and 25.1% of the remaining age groups tested positive for cocaine metabolites. Among specimens that tested negative with the screening assays, approximately 3% (182 specimens, with 15 from newborns) clearly contained detectable amounts (between 50 and less than 300 ng/mL) of benzoylecgonine by GC/MS, while less than 0.6% had detectable amounts (10-25 ng/mL) of PCP. The mothers of 7 of the 15 newborns also had detectable benzoylecgonine at various concentrations. This indicates that a lower screening cutoff concentration may be desirable for cocaine metabolites in hospitalized patients. Among those patients positive for cocaine metabolites or PCP, most were males between 20 and 39 years old. The urine drug concentrations in this population were 4-300 times greater than the cutoff concentrations for the screening assays.

Severe isopropanolemia without acetonemia or clinical manifestations of isopropanol intoxication.

This is the first reported case of severe isopropanolemia in a patient who did not experience associated clinical manifestations and acetonemia. The patient was found lying face down in a hotel lobby but at admission was alert and oriented to place and person. Toxicological analysis of the patient's serum revealed the presence of isopropanol at a concentration of 72 mmol/L. An increased serum osmolal gap (81 mOsm/kg) was also observed. The serum concentration of isopropanol decreased to 9.5 mmol/L 15.5 h after admission with an estimated half-life of elimination of 5-7 h. No serum acetone was detected throughout the patient's hospitalization. The identity of isopropanol was confirmed by gas chromatography/mass spectrometry. The patient remained awake and alert while in the hospital and was discharged 5 days after admission. These unusual findings raise some fundamental questions about the role of isopropanol conversion to acetone in the manifestation of symptoms usually associated with isopropanol intoxication.

Coincident Down's and Tourette syndromes: three case reports.

Three patients with Down's syndrome and coincident Tourette syndrome are presented. Two patients had trisomy for G-group chromosome and one patient had mosaic trisomy. All had characteristic features of Gilles de la Tourette syndrome with multiple motor and vocal tics. While Tourette syndrome has been reported in other chromosomopathies, this report appears to be the first to note an association with Down's syndrome. The authors hypothesize that neurotransmitter abnormalities existing in Down's syndrome may predispose such individuals to basal ganglia dysfunction and the subsequent development of tics. In particular, abnormalities in serotonin metabolism may be involved.

Social quotients of children with phenylketonuria before and after discontinuation of dietary therapy.

The records of 16 early-treated children with phenylketonuria (PKU) whose low-phenylalanine diets had been discontinued at an average age of 5.5 years were reviewed for evidence of deterioration in functioning. Measures of their medical and social status, namely, serum phenylalanine levels and Vineland Social Quotients, before and after diet discontinuation were investigated via repeated measures analyses of variance. Social quotients decreased significantly following discontinuation and were inversely correlated with serum phenylalanine levels.

Neurologic correlates of osteogenesis imperfecta.

The neurologic status of ten patients with osteogenesis imperfecta (OI) was evaluated. Four patients with mild OI (type I) had normal neurologic findings and normal computed tomographic scans. Three of these four patients had macrocephaly. All six patients with severe OI (type III) had cortical atrophy on computed tomographic scan and three were also macrocephalic.

Homogeneous clinical subgroups in children with Tourette syndrome.

The existence of two clinically homogeneous subgroups in Tourette syndrome, depending upon the presence or absence of migraine or a family history of migraine, is suggested. Patients with Tourette syndrome who have migraine (n = 18) were found to have a significantly higher prevalence of disorders of arousal--particularly sleepwalking and night terrors--as well as a higher prevalence of motion sickness than patients without migraine (n = 27). They were also significantly more likely to exhibit a co-occurrence of associated features (two or more) than the patients without migraine. Patients with Tourette syndrome who have not had migraine headaches but in whom there is a family history for migraine (n = 20) were shown to have an intermediate prevalence of associated symptoms. It is suggested that the differential association for these symptoms in patients with Tourette syndrome may reflect an underlying abnormality in function of two different neurotransmitter systems.

Somnambulism in children with Tourette syndrome.

A total of 171 children, 57 with Tourette syndrome, 57 with learning disabilities and the rest with seizure disorders, were studied to discover the incidence of somnambulism. Of the 13 identified sleepwalkers, 10 had Tourette syndrome. It is argued that this may be due to a disturbance in serotonin metabolism.

Tourette's syndrome and migraine.

Among 60 patients with Tourette's syndrome (TS), whose mean age was 11.9 years, migraine was prevalent in 26.6%. This figure is substantially greater than that reported for the general population of school-aged children (4.0% to 7.4%) or for two control groups consisting of children with seizure disorders (n = 72) and learning disabilities (n = 62). The prevalence rates for these two control groups were 11.3% and 8.0%, respectively. The hypothesis is offered that the coexistence of TS and migraine in a subgroup of children with TS may reflect a similar abnormality underlying both conditions; specifically, neurohumoral dysfunction involving serotonin metabolism.

Children with Tourette syndrome: results of psychological tests given prior to drug treatment.

There have been several recent reports on the neuropsychological integrity of children and adults with Tourette syndrome (TS). However, the possible effects of tic-controlling medications on the test performance of subjects have not been thoroughly investigated, although drugs commonly used in the treatment of TS, such as haloperidol, have been shown to affect learning and behavior. In this study, 10 children diagnosed as having Gilles de la Tourette syndrome were individually administered a battery of psychological tests prior to starting drug treatment. Since a wide range of deficits and processing inefficiencies has been reported in association with the psychological functioning of children with Tourette's disorder, the test battery used was designed to include both measures of contemporary global functioning and measures designed to focus upon particular functional areas. Data analyses revealed a number of specific impairments in TS children relative to age-appropriate levels and levels of global functioning (i.e., IQ scores). The study revealed a number of graphomotor, nonmotor visual-perceptual, and receptive verbal deficits. In addition, a high frequency (50%) of the sample manifested significant Verbal-Performance IQ discrepancies. Results of this study, on a population of nonmedicated TS children, substantiated and extended findings of several previous reports which identified a number of circumscribed weaknesses in the functioning of children with Tourette's disorder.

Disorders of arousal in Gilles de la Tourette's syndrome.

Disorders of arousal (somnambulism and night terrors) were significantly more common among children with Gilles de la Tourette's syndrome (n = 57) than among children with seizure disorders (n = 58) or learning disabilities (n = 53). Neurohumoral disturbances may account for the differences.

Coincident infantile autism and Tourette syndrome: a case report.

A 15-year-old boy who had been diagnosed as having infantile autism (IA) at two years of age was found to have Tourette Syndrome (TS) in adolescence. This case report represents the second coincident finding of IA and TS in an adolescent autistic boy. The implications of a co-occurrence of IA and TS are discussed in the light of our current understanding of abnormalities in neurotransmitter metabolism common to both conditions.

Self-recognition deficits in autism: syndrome-specific or general developmental delay?

Many reports can be found in the theoretical literature that refer to a lack of self-awareness or a failure to distinguish self from nonself as a characteristic of autistic children. The empirical literature also contains reports of behaviors in autistic children that have often been taken as reflective of a failure to differentiate self, i.e., pronominal reversal, gaze aversion. The present study investigated the development of self-recognition in 15 autistic children in an effort to determine whether failures of self-recognition were of possible diagnostic significance for the syndrome or rather were reducible to general indices of developmental function, i.e., mental age. Fifty-three percent of the sample showed clear self-recognition. On the basis of a developmental assessment and data from a teacher questionnaire, these children were found to be functioning at mental ages akin to developmental norms for self-recognition. Those who failed to show self-recognition had mental ages below the developmental level at which many children recognize themselves and significantly lower than those autistic children who showed self-recognition. The results suggest that even when autistic children fail to recognize their self-images, this failure can be taken not as evidence for a syndrome-specific deficit but as a reflection of a general developmental delay.

Childhood migraine and motion sickness.

The incidence of motion sickness among 222 children in four diagnostic categories--migraine, nonmigraine headaches, seizure disorders, and learning disabilities--was compared. Motion sickness was found to be an associated feature in 45% of the cases of childhood migraine, in contrast to a 5% to 7% incidence in the other groups. Therefore, it is suggested that motion sickness be regarded as an additional reliable minor criterion in the diagnosis of childhood migraine. Hypotheses of common central and peripheral mechanisms underlying both conditions are offered.