Prediction of carrier status in Duchenne dystrophy by creatine kinase measurement.

Serum creatine kinase (CK) was measured in 515 healthy white women and 28 obligate carriers for Duchenne muscular dystrophy. There was substantial overlap between the control and carrier populations. To analyze the impact of the degree of overlap, the predictive value of a CK result was determined by (1) using sensitivity and specificity analysis, which assumes dichotomization into a positive or negative result based on a particular cut-off value; and (2) using likelihood ratio analysis, which evaluates an individual result based on the continuum observed for control and carrier populations. There was no clinically important difference whether an observed 57% or a hypothetical 33% overlap between control and carrier results was used. Because of the substantial overlap, the CK test utility is limited to those suspected carriers whose results fall above the healthy population interval. A low CK result does not provide sufficient assurance of noncarrier status.

Glycopyrrolate treatment of chronic drooling.

OBJECTIVE: To describe the use of glycopyrrolate in the control of drooling in children and young adults with cerebral palsy and related neurodevelopmental disabilities. DESIGN: Prospective, open-label study of drug dosage parameters, response to therapy, and side effects. Follow-up ranged from 8 months to 4 years. SETTING: Outpatient clinic of a rehabilitation hospital that is a regional referral center for children with disabilities. PATIENTS: Forty children and young adults with motor and/or cognitive disabilities who were experiencing drooling to a severe degree. INTERVENTION: Treatment with oral glycopyrrolate. OUTCOME MEASURES: Change in the quantity of drooling and side effects associated with treatment. RESULTS: Thirty-six patients (90%) had reduced drooling in response to medication; 2 (5%) could not be assessed and 2 (5%) received no benefit. Side effects resulted in discontinuation of treatment in 11 (28%). Overall, 26 (65%) continued to receive drug therapy because of the perceived benefit. The final effective dose ranged widely from 0.01 to 0.82 mg/kg per day. CONCLUSIONS: Glycopyrrolate therapy safely and effectively decreased but rarely abolished drooling in patients with cerebral palsy and related neurodevelopmental disabilities. The dose range was surprisingly broad. Side effects, although generally minor and predictable, often led to discontinuation of drug therapy.

Autosomal dominant torsion dystonia with onset in infancy.

We report a man and his daughter who had onset of dystonia during the first year of life, primarily involving their legs and consisting of both sustained postures and rhythmical 2-3 Hz twisting movements. They also had eccentric and irregularly shaped pupils, but no other neurological abnormalities. This disorder differs from all familial dystonia syndromes described in the literature, including classic idiopathic torsion dystonia, which has a later age of onset. This disorder probably represents a new autosomal dominant dystonia syndrome.

Pitfalls in developmental diagnosis.

The more common and more glaring pitfalls in developmental diagnosis encountered during infancy and early childhood have been outlined. Much of the ability to avoid these traps depends on a comfortable understanding of the four spheres of early child development and a sound familiarity with the principles of developmental assessment, especially the separation of intellectual and motor entities. Motor milestones are excellent indicators of motor competence but correlate poorly with intellectual capacity. Language and problem-solving milestones in infancy provide the best insights into a child's intellectual potential, and their evolution is independent of motor competence. They may be obscured by motor disability and as a result may be more difficult to demonstrate, but that is a separate issue. In that instance there is nothing subtle about the fact that one is already dealing with a disabled infant. Psychosocial abilities (affective milestones) are critical in understanding the whole child and in making a meaningful statement about behavior, but they lend little additional information to the assessment of intellectual and motor competence. For physicians the "curb-side consult" is a highly efficient tool that has great practical application to developmental concerns and especially to the avoidance of the pitfalls described. Every practitioner should have a resource in developmental and behavioral pediatrics with whom he or she can communicate in an informal fashion. This is especially valuable in situations in which the urgency or even the need for referral (a time-consuming, expensive, and often anxiety-provoking process) is not clear.

Primitive reflexes. Their contribution to the early detection of cerebral palsy.

In evaluating the infant for significant motor impairment, a framework to organize and analyze data is presented. Five general areas of information are essential: (1) motor milestone attainment, (2) the classic neurological examination, (3) primitive reflex and postural reaction patterns, (4) progressive vs static nature of the dysfunction, and (5) associated evidence for neurological dysfunction and/or structural nervous system damage. A sixth criterion, age of onset, is relevant--but controversial--to making the specific diagnosis of cerebral palsy. The treatment of and prognosis for children with cerebral palsy have been linked to the historical and examination features outlined, particularly primitive reflexes. For the practicing pediatrician, understanding the fundamentals of the primitive reflex/postural reaction transition and achieving clinical facility with the elicitation of these signs represent skills that are readily acquired, easy to incorporate in routine clinical practice, and diagnostically useful.

Neurodevelopmental outcomes in congenital hypothyroidism: comparison of initial T4 dose and time to reach target T4 and TSH.

OBJECTIVES: To compare neurodevelopmental outcomes in severe and moderate congenital hypothyroidism (CH) among 3 different initial L-thyroxine doses and to examine the effect of the time to thyroid function normalization on neurodevelopmental outcomes. STUDY DESIGN: Neurodevelopmental assessments of 31 subjects included the Mullen Scales of Early Learning, Wechsler Preschool and Primary Scale of Intelligence-Revised, Wechsler Intelligence Scale for Children, Wide-Range Achievement Test, and Child Behavioral Checklist. RESULTS: Subjects started on higher initial L-thyroxine doses (50 mug) had full-scale IQ scores 11 points higher than those started on lower (37.5 mug) initial doses. However, verbal IQ, performance IQ, and achievement scores did not differ among the 3 treatment cohorts. Subjects with moderate CH had higher full-scale IQ scores than subjects with severe CH, regardless of the initial treatment dose. Subjects who took longer than 2 weeks to normalize thyroid function had significantly lower cognitive, attention, and achievement scores than those who achieved normal thyroid function at 1 or 2 weeks of therapy. CONCLUSIONS: Initial L-thyroxine dose and faster time to normalization of thyroid function are important to optimal neurodevelopmental outcome. In severe CH, it is important to choose an initial dose at the higher end of the recommended range to achieve these goals.

Movement disorder following herpes simplex encephalitis.

Two children, an eight-year-old girl and a seven-month-old boy, recovered from herpes simplex encephalitis with minimal neurological residua following acyclovir treatment. Subsequently, they experienced marked deterioration, interpreted as either recrudescent infection or a post-infectious phenomenon. Features of the deterioration included encephalopathy and hyperkinetic movement disorder. MRI studies showed extensive neocortical damage, without involvement of the basal ganglia, thalamus or subthalamic nuclei. With aggressive supportive care, both children made a slow, steady recovery over several months. This supportive care is best provided in a closely supervised interdisciplinary setting.

Deterioration of feeding behavior following surgical treatment of drooling.

Few adverse effects of the surgical treatment of drooling are reported in the literature. This report describes a young man with severe extrapyramidal cerebral palsy and profuse drooling whose oral feeding behavior deteriorated following bilateral submandibular gland excision and parotid duct rerouting. Before surgery the patient had safe, functional oral feeding skills, and eating was enjoyable. Following surgery he developed progressive feeding difficulties, weight loss, and aspiration pneumonia. His deterioration led to the placement of a feeding gastrostomy and the end of all oral feedings. Surgery had a disturbing and apparently irreversible negative impact on the patient's quality of life.

Literature for parents of children with cerebral palsy.

Educational literature on cerebral palsy, designed for parents' reference, was assessed by three reviewers for content and audience appeal. Of the 88 publications received, 47 were not pertinent to the topic and 11 were useful only for reading lists, bibliographies, etc. Of the other 30 publications, 18 were deemed not useful and many of these were inaccurate and misleading. Five publications were broadly useful and a further seven were useful in part or in specific situations.

Parents-as-teachers: design and establishment of a training programme for paediatric residents.

OBJECTIVES: To improve the training of paediatric residents in general and to provide more meaningful insights into family functioning. DESIGN: The programme is one facet of a 1-month developmental disabilities rotation for paediatric PL2 residents. It incorporates elements of family-centred care whereby physicians learn through home and community site visits about the importance of developing partnerships with parents and service providers in order to give better care to children with chronic conditions. SETTING: Gillette Specialty Health Care Center, St Paul, Minnesota. SUBJECTS: Paediatric PL2 residents and a parent group. RESULTS: Of 18 residents, 11 completed written and 18 completed oral feedback evaluations. There were infrequent but consistent complaints relating to logistics; more positive comments were made about the programme and individuals involved. CONCLUSIONS: In the minds of all participants, the Parents-as-Teachers (PAT) programme has been highly successful, as documented by short-term objective and subjective parent and resident feedback. The PAT experience represents a unique opportunity for parents and physicians-in-training to improve their mutual understanding. While not analysed in this report, the inclusion of a complementary programme involving on-site teaching in various community agencies also appears to be of value.

Use of DNA probes in detecting carriers of Duchenne muscular dystrophy: selected case studies.

Detection of Duchenne muscular dystrophy carriers by genetic analysis is illustrated by four case studies. The technique is most useful in obligate families, in excluding carrier status in isolated cases, and in families in which the affected child demonstrates a molecular deletion. A major limitation of this technique is that the accuracy of carrier status in isolated (i.e., no family history) cases is limited by the probability that the affected child may represent a new mutation. To improve the carrier risk estimate generated by the DNA data, particularly in isolated cases, we suggest that measuring creatine kinase activities in the serum and performing the genetic analysis on the nonaffected males may be helpful.

Practice parameter: diagnostic assessment of the child with cerebral palsy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.

OBJECTIVE: The Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society develop practice parameters as strategies for patient management based on analysis of evidence. For this parameter the authors reviewed available evidence on the assessment of a child suspected of having cerebral palsy (CP), a nonprogressive disorder of posture or movement due to a lesion of the developing brain. METHODS: Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a four-tiered scheme of evidence classification. RESULTS: CP is a common problem, occurring in about 2 to 2.5 per 1,000 live births. In order to establish that a brain abnormality exists in children with CP that may, in turn, suggest an etiology and prognosis, neuroimaging is recommended with MRI preferred to CT (Level A). Metabolic and genetic studies should not be routinely obtained in the evaluation of the child with CP (Level B). If the clinical history or findings on neuroimaging do not determine a specific structural abnormality or if there are additional and atypical features in the history or clinical examination, metabolic and genetic testing should be considered (Level C). Detection of a brain malformation in a child with CP warrants consideration of an underlying genetic or metabolic etiology. Because the incidence of cerebral infarction is high in children with hemiplegic CP, diagnostic testing for coagulation disorders should be considered (Level B). However, there is insufficient evidence at present to be precise as to what studies should be ordered. An EEG is not recommended unless there are features suggestive of epilepsy or a specific epileptic syndrome (Level A). Because children with CP may have associated deficits of mental retardation, ophthalmologic and hearing impairments, speech and language disorders, and oral-motor dysfunction, screening for these conditions should be part of the initial assessment (Level A). CONCLUSIONS: Neuroimaging results in children with CP are commonly abnormal and may help determine the etiology. Screening for associated conditions is warranted as part of the initial evaluation.

Are reference limits for serum creatine kinase valid in detection of the carrier state for Duchenne muscular dystrophy?

We evaluated serum creatine kinase (CK) as an index to heterozygosity in Duchenne muscular dystrophy. When the 97.5th percentile of the CK normal reference interval was selected as the cutoff point, only 31% of 28 obligate carrier mothers and 24% of 43 mothers of simplex cases (those with only one occurrence of dystrophy in the kindred) exceeded this cutoff value. The outcome depended to some degree on the method used for establishing the reference limit for 379 presumably non-carrier, ambulatory women. The considerable overlap of CK activities between the control and carrier population as well as the non-gaussian distribution of the data permitted no satisfactory approach for differentiating these two populations. Neither the application of likelihood ratios, which evaluates a continuum of results without the dichotomy of a cutoff point, nor the application of predictive value based on sensitivity and specificity, which involves use of a cutoff value for decision making, provided a reliable estimate of carrier status. There was no significant difference (2 alpha = .19) between the median CK activity of obligate carrier mothers and mothers of simplex cases. The serum CK test does not provide data that either support or reject the Haldane hypothesis.