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PubMed1987

Mianserin pharmacokinetics and behavior in hyperkinetic children.

The present study was conducted to derive pediatric mianserin pharmacokinetic parameters, which were compared to those from healthy young adults, and to obtain preliminary information regarding the utility of mianserin for the management of hyperkinesis in children. The sample consisted of six prepubescent children with hyperkinetic behavior disorders who had not responded, or had developed tolerance to, stimulant medication. Mianserin pharmacokinetics were derived from plasma samples obtained over a 36- to 50-hour period following a single oral dose which ranged from 0.28 to 0.72 mg/kg. Children evidenced a significantly faster elimination half-life and a significantly smaller apparent kinetic volume of distribution than did adults, whereas maximum plasma concentration, time to maximum concentration, and apparent oral plasma clearance were similar. Ratings of behavioral deviance were obtained from teachers and parents during placebo and mianserin titration to a maximum dose of 40 mg/day. Although half the children showed some decrease in hyperactivity ratings, the small sample size and high variability of response preclude conclusions regarding the efficacy of mianserin for childhood hyperkinesis. Possible side effects in our sample included akathisia, excitability, insomnia, and migraine-like headache, as well as cardiovascular effects of tachycardia and two instances of minor electrocardiographic change. Our pharmacokinetic findings will be of import should mianserin prove useful for such childhood disorders as depression and/or enuresis.(ABSTRACT TRUNCATED AT 250 WORDS)

Attention Deficit Disorder with Hyperactivity↗
PubMed1985

Comparison of segmental and global ejection fraction in ischaemic heart disease.

In order to evaluate whether segmental ejection fraction (SEF) is a better index of left ventricular (LV) performance than global ejection fraction (EF), 25 patients with significant coronary stenosis and normal EF were studied. SEF was estimated from the LV cineangiogram after dividing the LV into eight segments by means of a long axis and three equally spaced chords perpendicular to it. The area of a given segment was measured in the end-diastole and the end-systole and SEF was calculated by determining the percent decrease in area for each segment. 12 out of the 25 patients presented hypokinesis, akinesis or dyskinesis of at least two segments; the inferior apical and both diaphragmatic segments were the regions most frequently affected. In 7 patients, these abnormalities were compensated by hyperkinesis of two or three other segments, whereas in the remaining 5 patients contraction abnormalities were not accompanied by hyperkinesis in spite of a normal EF. It is concluded that SEF is a more sensitive index of regional LV function than EF in patients with ischaemic heart disease.

Coronary Disease↗
PubMedDate not supplied

[Stereotaxic surgery in the hyperkinetic form of infantile cerebral palsy].

The results of 67 stereotaxic operations performed in 60 patients for the hyperkinetic form of infantile cerebral paralysis are presented. The efficacy of dentatotomy is compared with that of thalamotomy. Thalamotomy is most effective in patients with hemiatetosis and choreoatetoid hyperkinesis. Dentatotomy resulted not only in a reduction of hyperkinesis, but also in a considerable alleviation of muscle spasticity. The destruction of the lateral part of nuclels dentatus caused predominantly a reduction of the muscle tone and of involuntary movements of the lower extremities, and--to a lesser degree--of the upper as well. The destruction of the medial part of the nucleus dentatus resulted in a clear reduction of muscle dystony in the trunk.

Adult↗
PubMed1993

[The painful leg and moving toe syndrome].

The paper reports a case of painful-legs-and-moving-toes syndrome in a 75-year-old woman who developed it after a paralytic ischias attack at the age of 70. The syndrome was characterized by persistent pains in distal parts of the legs and feet and constant involuntary flexion-extension wave-like toe movements. SSEP studies revealed a defect of conduction in high-speed myelinated fibers of the lumbo-sacral radices of both sides. A cortical motor potential corresponding to the toe hyperkinetic movement was present. It the base of the hyperkinesis a reflectory mechanism may underlie initiated from radiculo-spinal nociceptive systems disinhibited in consequence of the deficiency of inhibitory control from high speed rear column afferents. Neurophysiological data suggest participation of cerebral mechanisms in realization of the hyperkinesis.

Action Potentials↗
PubMed1998

[Frequency and current clinical diversity of cerebral cortical dysgenesis].

OBJECTIVE: The extended use of MRI has increased the number of patients diagnosed of cortical dysgenesis and has changed the clinical spectrum usually associated with this disorder. The aim of this study was to know the frequency and clinical variety of cortical dysgenesis in our current patient population. PATIENTS AND METHODS: All patients with dysgenesis of the neocortex or of the hippocampus, according to radiological or pathological features, were selected from the total number of patients attended during 1996 at an outpatient hospital-based neuropediatric clinic. Malformations of cerebellar cortex and neurocutaneous syndrome were excluded. RESULTS: Twenty-one patients (1.3% of all patients attended at the clinic) studied by MRI showed polymicrogyria (43%) which was of perisilvian localization in three patients, heterotopias (33%), dysplasia of the hippocampus (24%), agyria-pachygria (14%) and hemimegaencephalia (5%). Three patients underwent surgical interventions. Epilepsy was present in 90%, mental retardation in 68%, cerebral palsy 47%, infantile spasms 40%, microcephally 25%, autism 10%, hyperkinesis 5% and learning disabilities in 33% of those school age children free of mental retardation. CONCLUSIONS: The actual prevalence of cortical dysgenesis at our clinic is similar to that of neurodevelopmental impairments following birth-asphyxia (1.2%), amounting to two thirds of those following prematurity and to half of those following a brain injury of late prenatal onset. Except for the almost constant presence of epilepsy, especially infantile spasms, clinical symptomatology is diverse and occurs in a similar percentages in brain lesions acquired during labour or during late pregnancy. Hyperkinesis and autism have a similar prevalence to that seen in the total number of patients attended at the clinic during 1996.

Cerebral Cortex↗
PubMed1998

[Brain lesions of perinatal and late prenatal origin in a neuropediatric context].

INTRODUCTION: The obstetric and neonatal technological advances have changed the frequency and syndromic classification of perinatal brain lesions. OBJECTIVE: To study all prevalent patients during 1996, with perinatal or late intrauterine brain lesions, in the outpatient neuropediatric clinic at our hospital. METHODS: Selection of patients according to neuroimaging findings, and/or neurological sequela with documented perinatal antecedent. EXCLUSION CRITERIA: a normal MRI, brain lesions of doubtful origin, or uncertain sequela with normal CT or echography studies. Descriptive study, and also analytical, using logistic regression to study the relationship between antecedents and sequela. RESULTS: A total of 111 patients with: brain lesions due to hypoxic-ischemic encephalopathy (22 cases), lesions due to prematurity (29), late intrauterine infection or neonatal meningitis as the only cause of fixed neurological impairment (12), unexpected vascular brain lesions during the neonatal period (11), late intrauterine brain lesions (37). The neurological sequela observed were: cerebral palsy (68%), epilepsy (47%), mental retardation (45%), learning disorders in (34%) of those of school age and free from mental retardation, strabism (26%), microcephaly (19%), visual impairment (14%), hyperkinesis (10%). The neuroimaging findings were: focal lesions (45%), hydrocephaly (28%), intraventricular haemorrhage (22%), white matter lesions (24%), venous thrombosis (2%). The multivariable analysis showed, as the most noticeable finding, the relationship between the antecedent of mechanical ventilation and late development of hyperkinesis (OR: 10), in this sample of patients with severe sequela. Three patients should be noted: a case of late-onset dystonia secondary to a late intrauterine brain lesion, a child with exclusively cerebellar symptoms due to a destructive cerebellar lesion of prenatal onset, and a patient with an acquired perinatal biopercular lesion and pseudobulbar palsy as the only long-term sequelae.

Abnormalities, Multiple↗
PubMed1976

[Chorea minor under ovulation inhibitors].

Three weeks after commencing oral contraception for the first time, a 26-year-old woman with a history of rheumatic carditis and chorea minor presented with sudden recurrence of hyperkinesis. Withdrawal of the contraceptive agent was followed by rapid remission of the hyperkinesis, which suggests a casual relationship between the contraceptive and this condition and an analogy between this case and so-called chorea gravidarum. A young non-pregnant woman presenting with chorea minor should be specifically questioned by ingestion of oral contraceptives. If there is a past history of rheumatic fever with or without chorea, oral contraceptives are contraindicated.

Adult↗
PubMed1980

Paradoxical effects of d-amphetamine upon seizure susceptibility in 2 selectively bred lines of mice.

The ontogeny and substrates of amphetamine-induced changes in flurothyl-induced myoclonic and clonic seizure thresholds were investigated in 2 selectively bred lines of mice. The long-sleep mice exhibited dose-dependent increases in myoclonic and clonic susceptibility following amphetamine, irrespective of age. The noradrenergic agonist clonidine and the dopaminergic agonist apomorphine produced increases in susceptibility comparable to those seen with amphetamine. The short-sleep mice, however, exhibited a dichotomous myoclonic response to amphetamine that was age-dependent. Between 15 and 35 days of age amphetamine decreased seizure susceptibility whereas increases in susceptibility were noted at later ages. With the exception of 80 days, amphetamine did not affect clonic thresholds. In respect to myoclonus, clonidine persisted in producing effects similar to those seen in the long-sleep mice whereas apomorphine exhibited the same ontogenetic alteration in effect seen with amphetamine. These results confirm that the short-sleep mice might be a naturally occurring animal model of preadolescent hyperkinesis. Furthermore, the neuropharmacological tests demonstrate that the paradoxical response to amphetamine in the young short-sleep mice is mediated via a dopaminergic mechanism that must undergo dramatic change during ontogeny.

Age Factors↗
PubMed1988

4-Hydroxybutyric aciduria in a patient without ataxia or convulsions.

A child presenting with mild psychomotor retardation, hypotonia, microcephaly and hyperkinesis is described. Urinary organic acid analysis by combined gas chromatography-mass spectrometry revealed 4-hydroxybutyric aciduria. Succinic semialdehyde dehydrogenase activity in extracts of white cells derived from the patient was less than 10% of control values.

Ataxia↗
PubMed1979

Rating scales for hyperactivity: concurrent validity, reliability, and decisions to label for the Conners and Davids Abbreviated Scales.

Rating scales have become the instrument of choice in labeling and assessing change in behavior of hyperactive children. However, several criticisms have recently have levied against their use. The present investigation examined the concurrent validity, and inter- and intrarater reliability for the Abbreviated Teacer Questionnaire (ATQ, Conners, 1973) and the Rating Scales for Hyperkinesis (Davids, 1971). Sixteen teachers from two special and two regular schools (grades 1-4) rated 211 normal and 49 special children using both scales. High correlations were found suggesting excellent predictability between scales and considerable stability across time and rater. Lower scores on a subsequent rating relative to an initial rating were demonstrated, dependent on time between ratings but independent of (a) teacher expectation of treatment gains, (b) bias produced by rating selected children, and (c) whether children were hyperactive or normal. Use of initial and infrequent rating scores versus subsequent, closely spaced ratings was related to the rater's objective (e.g., diagnosis, treatment, or assessment).

Child↗
PubMed1981

Hyperactive and aggressive behaviors in childhood: intertwined dimensions.

The relationship between aggression and hyperactivity is unclear in childhood hyperkinesis. To examine the relationship between the two dimensions, a sample of 109 first-, second-, and third-grade children who were rated as hyperactive were evaluated daily by their teachers for 12 consecutive school days on the Daily Behavior Checklist. Daily recordings were made on a total of 22 specific behaviors, 11 physically or verbally aggressive acts, and 11 acts of a restless or hyperactive nature. The Conners hyperactivity score correlated .47 with daily aggression and .49 with daily hyperactivity. A subgroup of hyperactive children who exhibited both hyperactive and aggressive behaviors at rates greater than 98% of their classmates was selected. These children were rated significantly higher on the Conners scale than on alternate subgroup of hyperactive children who showed high rates of hyperactive but not aggressive behaviors. In view of heavy reliance on teacher ratings with the Conners scale in studies of hyperactivity, careful consideration of the potential confounding of hyperactivity and aggression is recommended. Implications for classification, longitudinal investigation, and evaluation of treatment of hyperactive children were discussed.

Age Factors↗
PubMed1976

EEG and behavioral changes in a hyperkinetic child concurrent with training of the sensorimotor rhythm (SMR): a preliminary report.

Reduced seizure incidence coupled with voluntary motor inhibition accompanied conditioned increases in the sensorimotor rhythm (SMR), a 12- 14 Hz rhythm appearing over rolandic cortex. Although SMR biofeedback training has been successfully applied to various forms of epilepsy in humans, its potential use in decreasing hyperactivity has been limited to a few cases in which a seizure history was also a significant feature. The present study represents a first attempt to explore the technique's applicability to the problem of hyperkinesis independent of the epilepsy issue. The results of several months of EEG biofeedback training in a hyperkinetic child tend to corroborate and extend previous findings. Feedback presentations for SMR were contingent on the production of 12- 14-Hz activity in the absence of 4- 7-Hz slow-wave activity. A substantial increase in SMR motor inhibition, as gauged by laboratory measures of muscular tone (chin EMG) and by a global behavioral assessment in the classroom. Opposite trends in motor inhibition occurred when the training procedure was reversed and feedback presentations were contingent on the production of 4- 7 Hz in the absence of 12- 14-Hz activity. Although the preliminary nature of these results is stressed, the subject population has recently been increased to establish the validity and generality of the findings and will include the use of SMR biofeedback training after medication has been withdrawn.

Biofeedback, Psychology↗
PubMed1979

Dietary management of nystagmus.

Two case reports illustrate the therapeutic response of congenital nystagmus to a diet eliminating synthetic food colors, synthetic food flavors, the antioxidant preservatives butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA), and a small group of foods thought to contain a natural salicylate radical. A brief discussion of the hyperkinetic syndrome is offered with the proposal that a variety of neurologic and neuromuscular disturbances (grand mal, petit mal, psychomotor seizures; La Tourette syndrome; autism; retardation; the behevioral component of Down's syndrome; and oculomotor disturbances) may be induced by identical chemicals, depending upon the individual's genetic profile and the interaction with other environmental factors. It is perhaps the failure to integrate all the signs presented by the various clinical patterns with hyperkinesis or Minimal Brain Dysfunction (MBD) under a single heading that eye muscle involvement manifested as either nystagmus or strabismus has not been emphasized as part of the hyperkinetic syndrome.

Child, Preschool↗
PubMed1976

The hyperkinetic child syndrome: the need for reassessment.

The dramatic increase in the incidence of hyperkinesis witnessed in recent years constitutes a growing concern for the children so classified. Some relevant issues are discussed in terms of (a) diagnostic practices, (b) treatment practices, and (c) changing views about the nature of the disorder itself. Rather than focusing on the child as a source of the problem (as has typically been the case), future research and practices need to demonstrate a broad-based perspective on the adjustment problems of these children that examines "situational" determinants and institutional policies.

Amygdala↗
PubMed1995

Hyperthermia following MDMA administration in rats: effects of ambient temperature, water consumption, and chronic dosing.

In two experiments it was found that the hyperthermia which follows MDMA ("Ecstasy") results from an interaction of direct pharmacological effect of the drug and the prevailing environmental conditions in which it is administered. In Experiment 1, rats given fixed doses of either 2.5, 5.0 or 7.5 mg/kg MDMA or saline were injected on different days at ambient temperatures (Ta's) of 11, 24, and 30 degrees C. At each Ta drinking water was freely available following dosing on one session and temporarily unavailable on a second. The hyperthermic and hyperkinetic responses were monitored using remote biotelemetry. Experiment 2 used a between-subject design in which each group of rats received a standard 7.5 mg/kg dose of MDMA administered at only one of the three levels of Ta(24 degrees C) and at only one level of the water-availability factor. Dosing in some groups was continued for a further 13 days to test for tolerance or sensitization effects. Ambient temperature significantly affected the magnitude of the hyperthermia but not the hyperkinesis. Water deprivation during the drugged period significantly augmented the hyperthermia, but only in the high Ta (30 degrees C.) condition. Chronic dosing produced sensitization of both hyperthermic and hyperkinetic responses. The findings indicate that ambient temperature, water consumption and frequency of drug use affect the hyperthermia which follows MDMA administration.

Animals↗
PubMed1999

Transgenic rescue of SNAP-25 restores dopamine-modulated synaptic transmission in the coloboma mutant.

Many of the molecular components constituting the exocytotic machinery responsible for neurotransmitter release have been identified, yet the precise role played by these proteins in synaptic transmission, and their impact on neural function, has not been resolved. The mouse mutation coloboma is a contiguous gene defect that leads to electrophysiological and behavioral deficits and includes the gene-encoding SNAP-25, an integral component of the synaptic vesicle-docking/fusion core complex. The involvement of SNAP-25 in the hyperactive behavior of coloboma mice, which can be ameliorated by the indirect dopaminergic agonist, amphetamine, has been demonstrated by genetic rescue using a SNAP-25 transgene. Coloboma mice also exhibit increased recurrent inhibition, reduced theta rhythm by tail-pinch and reduced long-term potentiation in the hippocampal dentate gyrus that, as the hyperkinesis seen in these mutants suggests, may reflect impaired monoaminergic modulation. We sought to identify neurophysiological correlates of the rescued hyperactivity within hippocampal synaptic circuitry of SNAP-25 transgenic coloboma mutant mice. In contrast to the differences between coloboma and wild-type mice, there was no significant difference in the duration or amplitude of theta rhythmic activity (4-6 Hz) induced by tail-pinch (10 s), afferent-evoked field potentials, or paired-pulse responses recorded in the dentate gyrus of SNAP-25 transgenic coloboma and wild-type mice. Amphetamine (3.0 mg/kg, i.p.) produced disinhibition of dentate paired-pulse responses in both SNAP-25 transgenic and wild-type mice but increased inhibition in non-transgenic coloboma mice. These findings support the hypothesis that alteration of monoaminergic neurotransmission, which can be reversed by the indirect agonist, amphetamine, is particularly sensitive to alterations in the expression of SNAP-25.

Amphetamine↗
PubMed1980

Gas chromatographic/mass spectrometric analysis of methylphenidate (ritalin) in serum.

A gas chromatographic/mass spectrometric (GG/MS) procedure for the determination of methylphenidate in 1 mL of serum or plasma is reported employing ethylphenidate as internal standard. A 50/50 (V/V) mixture of benzene and hexane is used to extract the methylphenidate and ethylphenidate from plasma. After evaporation of solvent the residue is redissolved in 50 microL hexane. Methyl- and ethylphenidate are then derivatized by the addition of 50 ML of trifluoroacetic anhydride and the TFA derivatives are injected into a quadrupole GC/MS for analysis. This method has a lower limit of sensitivity for methylphenidate of 2.0 micrograms/L. The between-day precision study yielded coefficients of variation of 10.4% and 14.8% at methylphenidate concentrations of 25.6 and 5.2 micrograms/L respectively. The assay has been used to investigate the pharmacokinetics of methylphenidate administered to 6 children for treatment of hyperkinesis. The study yielded ranges for volume of distribution, elimination half-life, and total body clearance of 5.0-6.8 L/kg, 1.6-2.7 hours, and 1.4-2.9 L/kg-hr respectively.

Adolescent↗
PubMed1977

Vaccination against whooping-cough. Efficacy versus risks.

Calculations based on the mortality of whooping-cough before 1957 predict accurately the subsequent decline and the present low mortality. Notifications of incidence, though variable and incomplete, follow the same pattern of steady decline in the United Kingdom and are unaffected either by small-scale vaccination beginning about 1948 or by nationwide vaccination beginning in 1957. When valid comparisons can be made, attack-rates may be lower and complications fewer in vaccinated children, but allowance has to be made for overcrowding and socio-economic differences which may be more important as determinants of attack-rates. No protection by vaccination is demonstrable in infants. Adverse reactions and neurotoxicity following vaccinations were studied in 160 cases. In 79, the relationship to pertussis vaccine was strong. In 14 of these cases, reaction was transient but characteristic of a syndrome of shock and cerebral disturbance, which, in the other 65 cases, was followed by convulsions, hyperkinesis, and severe mental defect. It seems likely that most adverse reactions are unreported and that many are overlooked. Precise information about the efficacy and safety of this vaccine is lacking, because existing provisions, national and international, for epidemiological surveillance and evaluation are inadequate. The claim by official bodies that the risks of whooping-cough exceed those of vaccination is questionable, at least in the U.K.

Adolescent↗