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Biomedical subjects

H S Singer

Publications and source records attributed to H S Singer.

At least 55 records · Page 3Linked to original sources

Executive function in children with Tourette syndrome and/or attention deficit hyperactivity disorder.

Tourette Syndrome (TS) in children is associated with various neurobehavioral disorders including attention deficit hyperactivity disorder (ADHD). Children with TS and ADHD show some difficulties with neuropsychological tasks, but we do not know if children with TS alone have neuropsychological deficits. To assess specific cognitive differences among children with TS and/or ADHD, we administered a battery of neuropsychological tests, including 10 tasks related to executive function (EF), to 10 children with TS-only, 48 with ADHD-only, and 32 with TS + ADHD. Children in all groups could not efficiently produce output on a timed continuous performance task [Test of Variables of Attention (TOVA) mean reaction time and reaction time variability]. Children with TS-only appeared to have fewer EF impairments and significantly higher perceptual organization scores than children with TS + ADHD or ADHD-only. These findings suggest that deficiencies in choice reaction time and consistency of timed responses are common to all three groups, but children with TS-only have relatively less EF impairment than children with TS + ADHD or ADHD-only.

Adolescent↗

Learning difficulties in children with Tourette syndrome.

Children with Tourette syndrome have been shown to have a variety of school difficulties. These difficulties, however, may be related to a single factor or to a combination of problems including tic severity, the use of tic-suppressing medication, executive dysfunction, a direct consequence of having a stigmatizing disorder, and coexisting attention deficit disorder, hyperactivity, obsessive-compulsive behaviors, or other psychopathologies. The goals for the treating health care team are to identify the presence of these factors, to clarify which are the major source of distress, and to develop an individualized multimodal treatment program. The prompt diagnosis of underlying problems and the prescription of appropriate therapy can play an important role in preventing school failure in children with Tourette syndrome.

Adrenergic alpha-Agonists↗

The treatment of attention-deficit hyperactivity disorder in Tourette's syndrome: a double-blind placebo-controlled study with clonidine and desipramine.

OBJECTIVES: Because psychostimulants can exacerbate preexisting motor/phonic tics in individuals with Tourette's syndrome (TS), a clinical trial was performed to examine the ability of clonidine and desipramine to modify attention-deficit hyperactivity disorder (ADHD) behaviors in children with TS + ADHD. METHODS: A double-blind, placebo-controlled protocol was used in which each subject served as his or her own control and received, in a randomly assigned fashion, 6-week medication cycles with clonidine (0.05 mg four times daily), desipramine (25 mg four times daily), and placebo. RESULTS: Thirty-seven children with TS+ADHD between the ages 7 to 13 years and of normal intellect were recruited, and 34 (31 males, 3 females) completed the entire protocol. Outcome measures for ADHD included Parent and Teacher Child Behavior Checklists (CBCL), continuous performance tests, and neuropsychologic tests of executive function. Several markers for ADHD were shown to improve significantly (P < .05) after treatment with desipramine (parent linear analogue rating, parent CBCL "hyperactivity" subscale, and teacher CBCL subscales "nervous/overactive," "anxious," and "unpopular"). Improvement with desipramine was always superior to that noted with clonidine. Clinical improvement did not correlate with drug blood levels. On measures of tic severity, neither drug made tics worse. Desipramine showed a statistically significant improvement on a global linear analogue scale, but not on the Hopkins Motor/Vocal Tic Severity Scale, the Tourette Syndrome Severity Scale, or the Yale Global Tic Severity Scale. Clonidine did not significantly alter tic severity on any measure. CONCLUSION: The results of this study suggest that desipramine may be a useful alternative for the treatment of symptoms of ADHD in children with TS.

Adolescent↗

Anti-Hu antibody in a neuroblastoma-associated paraneoplastic syndrome.

A 20-month-old infant with Turner syndrome presented with opsoclonus-myoclonus and tonic pupils in association with an abdominal neuroblastoma. Despite complete removal of the tumor, the child developed progressive hearing loss, areflexia, and seizures. Immunohistochemical and Western blot studies of serum and cerebrospinal fluid revealed the presence of anti-Hu antineuronal antibody, which cross-reacted with areas of the patient's tumor. Treatment with intravenous immunoglobulin coincided with the resolution of opsoclonus-myoclonus and the cessation of new neurologic symptoms. This case provides direct support for the autoimmune basis of paraneoplastic symptoms associated with neuroblastoma and suggests that treatment with intravenous immunoglobulin may be of value.

Abdominal Neoplasms↗

Migraine headaches in children.

Migraine headaches are common in children and adolescents, and stricter diagnostic criteria have been developed. Children have a variety of migraine syndromes, ranging from frequent, mild, bifrontal headaches to severe debilitating, unilateral pain associated with persistent motor or visual deficits. Neurodiagnostic studies are indicated in those individuals who have accompanying signs or symptoms that raise concern. The treatment of migraine must be individualized and requires more than just the use of pharmacotherapy. Reassurance and the elimination of potential triggering factors are essential components of care. Symptomatic therapy with analgesics and rest often is sufficient. Behavioral therapy, consisting of psychological support, relaxation exercises, and biofeedback training, is effective in reducing the frequency and severity of migraine. Ergotamines are valuable agents for abortive treatment, but should be reserved for use in the older child. Parenteral use of DHE is an effective treatment for the rare child who has an acute severe migraine unresponsive to other therapies. A variety of agents are available for the long-term stabilization of childhood migraine.

Analgesics↗

Self-reporting of behavior problems in patients with tic disorders.

Self-awareness of behavioral or emotional problems was examined in 25 children and adolescents with tic disorders by comparing the Youth, Parent, and Teacher forms of the Child Behavior Checklist. In general, their parents reported a significant number of deviant behaviors which were denied by the patients.

Adult↗

Advances in understanding the development of the nervous system.

Over the past several years remarkable progress has been made towards unraveling the complex mechanisms that regulate neuronal development. Because the end results of abnormalities in brain development are often developmental disabilities, it is timely to review several recent advances in the field of neurobiology. This review, with contributions from several co-authors, provides a synopsis of breakthroughs from the fields of embryology, cell biology, and molecular genetics that hold promise for exciting clinical application. This article is arranged to reflect the stages of normal development. Understanding the mechanisms underlying neuronal induction, regional specification, neuronal specification, migration, axonal growth, neurotrophic factors, and myelination should clarify the pathophysiology of numerous neurological disorders, and provide new insights into their treatment.

Animals↗

Volumetric MRI changes in basal ganglia of children with Tourette's syndrome.

To define the site of pathology in Tourette's syndrome (TS), we performed a volumetric MRI study of basal ganglia structures and lateral ventricles on 37 children with this disorder and 18 controls. There were no statistically significant differences in the size of the right or left caudate, putamen, globus pallidus, or ventricles in these populations. In contrast, there were significant differences for measures of symmetry in the putamen and the lenticular region. Virtually all controls (17 right- and one left-handed) had a left-sided predominance of the putamen, whereas in 13 of 37 TS subjects, a right predominance exceeded that of any control. Statistical comparisons among TS patients, with (n = 18) or without (n = 19) attention-deficit hyperactivity disorder (ADHD), and controls showed significant differences for the volume of the left globus pallidus and for lenticular asymmetry. Post hoc evaluations showed that in the TS + ADHD group, the volume of the left globus pallidus was significantly smaller than the volume of the right and that lenticular asymmetry was due to a greater right-sided predominance in the TS+ADHD group. This study lends further support to proposals that claim the basal ganglia is involved in the pathogenesis of TS and also suggests that the comorbid problem of ADHD is related to regional changes that differ from those primarily associated with tics.

Adolescent↗

Tic disorders.

This article has provided an approach to patients who present with Tourette's syndrome or other tic disorders. The goals are to clarify each of the problems, to determine whether the major source of distress is related to tics or associated behaviors, and to develop an individualized multimodal treatment program. A valuable source of additional information for physicians, parents, and patients is the voluntary nonprofit Tourette Syndrome Association, 42-40 Bell Blvd, Bayside, NY 11361-9596.

Antipsychotic Agents↗

The validity of instruments measuring tic severity in Tourette's syndrome.

By using four different scales that measure tic severity in Tourette's syndrome, three independent judges concurrently evaluated their validity and interjudge reliability in 20 affected individuals. The Yale Global Tic Severity Scale, Tourette's Syndrome Severity Scale, Tourette's Syndrome-Clinical Global Impression Scale, and the Hopkins Motor and Vocal Tic Scale were equally effective in determining overall severity and showed good interrater reliability. Both historical information and direct observation of the subject were shown to have a significant contribution towards the overall assessment of tic severity. With all instruments, tic symptom ratings were shown to be independent of those for either attention-deficit hyperactivity disorder or obsessive-compulsive disorder. A 67% incidence of behavioral problems and social difficulties was identified by the Child Behavior Checklist. Nevertheless, associations with tic severity were limited to areas showing interference with social relationships and school adjustments. These results extend the understanding of Tourette's syndrome severity scales and provide additional information necessary for the development of a unified rating scale.

Adolescent↗

Chronic recurrent headaches in children.

Chronic recurrent headaches in children can be classified into distinct categories based on a careful history and physical examination. Migraine and muscle contraction headaches are common in the pediatric population. Laboratory studies should be limited to those individuals who have other signs or symptoms accompanying headaches that raise concern. Reassurance about the underlying pathophysiology of vascular or muscle contraction headaches, their benign nature, and favorable prognosis may not only relieve associated anxiety that may produce or prolong headache, but also may relieve the headache itself. Symptomatic mild analgesics and behavioral medicine therapy are often sufficient, although occasionally prophylactic pharmacotherapy is required. The long-term prognosis for children with chronic recurrent headaches is generally favorable.

Age Factors↗

Abnormal dopamine uptake sites in postmortem striatum from patients with Tourette's syndrome.

The dopamine hypothesis for Tourette's syndrome proposes that the disorder is pathologically related either to an excessive amount of dopamine or to supersensitive receptors. To evaluate these proposals, pre- and postsynaptic markers of dopamine metabolism were measured in postmortem striatum from three adults with the diagnosis of Tourette's syndrome. Neuronal dopamine uptake carrier sites [( 3H]mazindol binding) were significantly increased in number over control values by 37% in the caudate and by 50% in the putamen. High-pressure liquid chromatographic assays of dopamine and its primary metabolites, homovanillic acid and 3,4-dihydroxyphenylacetic acid, showed normal findings. D1 and D2 subtypes of dopaminergic receptors [( 3H]SCH 23390 and [3H]spiperone binding, respectively) showed only slight alterations, presumably due to treatment with neuroleptics. The concentration of adenosine 3',5'-monophosphate (cyclic AMP) in putamen was reduced by 23%. Our data support earlier proposals of a dopaminergic abnormality in TS, but suggest that the mechanism involves a significant alteration of uptake sites. We speculate that increases in carrier site binding indicate an enhanced dopamine innervation within the striatum.

3,4-Dihydroxyphenylacetic Acid↗

Tourette syndrome and other tic disorders. Diagnosis, pathophysiology, and treatment.

In this report, we discuss the definition, characteristics, pathophysiology, and treatment of tic disorders with a major emphasis on Tourette syndrome. Although the diagnosis of a tic disorder depends on the presence of motor and/or phonic tic(s), patients with these problems also have a variety of co-morbid features including obsessive-compulsive symptoms, attention-deficit hyperactivity disorder, behavioral difficulties, and learning disabilities. Conservative estimates for Tourette syndrome suggest a prevalence rate of 0.1-1.0 per 1000. This syndrome is inherited in a sex-influenced autosomal dominant pattern with either chronic multiple tic disorder or obsessive-compulsive disorder as alternative phenotypes of the putative gene. Current evidence continues to support a pathophysiologic mechanism involving synaptic neurotransmission, with the dopaminergic system as a primary candidate. Therapeutically, it is essential to clarify whether a patient's problems are related to tics or associated behavioral difficulties. Pharmacotherapy for motor and phonic tics is strictly symptomatic and should be reserved for those with functionally disabling symptoms. A comprehensive individualized treatment program is often required in the care of individuals with tic disorders.

Behavior↗

Postencephalitic acquired Tourette-like syndrome in a child.

We report a 6-year-old girl who developed a Tourette-like syndrome following presumed herpes encephalitis. This case suggests that tics can be acquired in childhood and may be associated with lesions involving basal ganglia or limbic circuitry.

Child↗

The effect of aluminum on markers for synaptic neurotransmission, cyclic AMP, and neurofilaments in a neuroblastoma x glioma hybridoma (NG108-15).

The effects of the neurotoxin aluminum on markers of synaptic neurotransmission, adenosine 3',5'-monophosphate, and neurofilaments have been evaluated in a neuroblastoma x glioma hybridoma (NG108-15). Cells were exposed for 4 days to 2 mM aluminum lactate, a concentration that did not suppress growth. Compared to controls, the activity of choline acetyltransferase was significantly increased by 37% associated with an up-regulation in enzyme activity (Vmax). Muscarinic receptors, measured by [3H]QNB binding, were reduced by 41%. In contrast, the activities of acetylcholinesterase and glutamate decarboxylase were not significantly changed. Aluminum raised the level of cyclic AMP by 20%, although adenylate cyclase activity was unchanged. Small amounts of both phosphorylated and non-phosphorylated neurofilaments were detected in NG108-15 cells. Aluminum intoxication, however, did not alter the quantity, ultrastructure, or immunoreactivity of neurofilaments. Our results demonstrate the capability of aluminum to produce selected changes in cholinergic markers and levels of cyclic AMP in a rapidly dividing cell line.

Aluminum↗