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Biomedical subjects

Donald L Gilbert

Publications and source records attributed to Donald L Gilbert.

25 records · Page 2Linked to original sources

Transcranial magnetic stimulation in children.

Single and paired pulse transcranial magnetic stimulation (TMS) provide a non-invasive, painless method of probing the motor system. These techniques are of particular interest for studying maturation of the motor system and may provide insights into those developmental disabilities strongly associated with specific delays of motor development. This article will review studies using single pulse and paired pulse TMS in children, with particular reference to insights into neurodevelopment in children. It will also briefly touch on the potential of TMS as a diagnostic tool in neurological disorders. It will not address the use of repetitive TMS in children.

Adolescent↗

Tic reduction with risperidone versus pimozide in a randomized, double-blind, crossover trial.

OBJECTIVE: To compare the tic suppression, electrocardiogram (ECG) changes, weight gain, and side effect profiles of pimozide versus risperidone in children and adolescents with tic disorders. METHOD: This was a randomized, double-blind, crossover (evaluable patient analysis) study. Nineteen children aged 7 to 17 years with Tourette's or chronic motor tic disorder were randomized to 4 weeks of treatment with pimozide or risperidone, followed by the alternate treatment after a 2-week placebo washout. The primary efficacy outcome measure was change in tic severity assessed by the Yale Global Tic Severity Scale (YGTSS). ECG results, weight gain, and side effects were also compared. RESULTS: Compared to pimozide treatment, risperidone treatment was associated with significantly lower tic severity scores (YGTSS: baseline 43.3 +/- 17.5, pimozide 34.2 +/- 14.2, risperidone 25.2 +/- 13.6; p =.05). Weight gain during the 4-week treatment periods was greater for risperidone (mean 1.9 kg) than pimozide (1.0 kg). No patient suffered a serious adverse event, but 6 of 19 subjects failed to complete the protocol. Neither medication was associated with ECG changes. CONCLUSIONS: In this study, risperidone appeared superior to pimozide for tic suppression but was associated with greater weight gain.

Adolescent↗

Does sleep or sleep deprivation increase epileptiform discharges in pediatric electroencephalograms?

OBJECTIVE: Sleep deprivation before obtaining an electroencephalogram (EEG) is believed both to increase the likelihood of sleep during an EEG and to increase the detection of interictal epileptiform discharges. However, depriving a child of sleep poses a burden on both the parent and the child. The objective of this study was to compare the effects of sleep, standard sleep deprivation, partial sleep deprivation, and no sleep deprivation on the odds of an epileptiform abnormality in outpatient pediatric EEGs. METHODS: Data were collected from all pediatric EEGs performed at a busy, university-based neurologic practice during two 2-month periods. During the first period, all EEGs were performed as ordered, either standard sleep-deprived (SSD) or non-sleep-deprived (NSD). During the second 2 months, SSD EEGs were performed per routine. However, non-SSD families were instructed to keep their children awake 2 hours later the night before the EEG. Those who complied were classified as partially sleep-deprived (PSD). Patient characteristics across protocols were compared with chi(2) and analysis of variance tests as appropriate. The odds of epileptiform and abnormal findings associated with sleep, NSD, PSD, and SSD EEGs were calculated using logistic regression. RESULTS: Of 820 eligible EEGs, sleep occurred in 22% of NSD, 44% of PSD, and 57% of SSD EEGs. The sample size of this study allowed for an 85% power, with alpha of.05, to detect an absolute increased EEG yield of 10%. Neither the presence of sleep (odds ratio [OR]: 0.99; 95% confidence interval [CI]: 0.69-1.42) nor the use of PSD (OR: 0.90; 95% CI: 0.50-1.62) or SSD (OR: 0.96; 95% CI: 0.63-1.47) protocols increased the odds of epileptiform EEGs. CONCLUSIONS: Sleep deprivation should not be used routinely to increase the yield of pediatric EEGs.

Adolescent↗

Meta-analysis of EEG test performance shows wide variation among studies.

BACKGROUND: EEG results are used for counseling patients with seizures about prognosis and deciding on medications. Published sensitivities of interictal EEG vary widely. OBJECTIVE: To account for variation in test characteristics between studies. METHODS: Meta-analysis. Medline search, 1970 to 2000, of English language studies. Standard methods for meta-analysis of diagnostic test performance were used to determine the ability of EEG results to distinguish between patients who will and will not have seizures. Using linear regression, the authors assessed the influence of readers' thresholds for classifying the EEG as positive, sample probability of seizure, percent of subjects with prior neurologic impairment, percent treated, and years followed. RESULTS: Twenty-five studies involving 4,912 EEG met inclusion criteria. Specificity (range 0.13 to 0.99) and sensitivity (range 0.20 to 0.91) of epileptiform EEG interpretations varied widely and were heterogeneous by chi(2) analysis (p < 0.001 for each). Diagnostic accuracy of EEG and the thresholds for classifying EEG as positive varied widely. In the multivariate model, differences in readers' thresholds accounted for 37% of the variance in EEG diagnostic accuracy, and no other reported factors were significant. CONCLUSION: This analysis suggests that there is wide interreader variation in sensitivity and specificity of EEG interpretations, and that this variation influences the ability of EEG to discriminate between those who will and will not have seizure recurrences. In clinical practice, interpreting the degree to which a positive EEG result predicts increased seizure risk in an individual patient is difficult. Interpreting EEG with higher specificity yields more accurate predictions.

Adult↗

Pharmacodynamics of ziprasidone in children and adolescents: impact on dopamine transmission.

OBJECTIVE: Ziprasidone is an atypical antipsychotic with a high ratio of 5-HT(2A) to D(2) receptor antagonism. It is also an agonist at 5-HT(1A), which has been shown in rats to increase dopamine in prefrontal cortex. The objective of this study was to probe the dopamine agonist and antagonist pharmacodynamic properties of ziprasidone in youth. METHOD: A single-dose, open-label study was conducted in 24 youths, 7 to 16 years of age, with Tourette syndrome or chronic tic disorder. Ziprasidone oral suspension (40 mg/mL) was given to achieve 0.2 to 0.3 mg/kg. Patients were subsequently assessed for serum ziprasidone, serum prolactin, and eye blink rates. RESULTS: Serum ziprasidone peaked 4 hours postdose. Prolactin (baseline mean 7.2 ng/mL, 95% confidence interval [CI] 5.2-9.2) peaked at 4 hours (mean 27.5 ng/mL, 95% CI 22.6-32.3). Eyeblink rates per 5 minutes (baseline mean 60, 95% CI 42-79) peaked at 6 hours (mean 74, 95% CI 52-96). CONCLUSIONS: Ziprasidone acutely blocks dopamine transmission, as indicated by increased prolactin levels, and, in a delayed fashion, appears to stimulate dopaminergic transmission, as indicated by the increase in spontaneous eye blinks. The mechanism of dopaminergic stimulation is presumed to be indirect, via 5-HT(1A) agonism.

Adolescent↗

Genomic abnormalities in patients with migraine and chronic migraine: preliminary blood gene expression suggests platelet abnormalities.

BACKGROUND: Migraine has strong genetic and environmental components and may also be a significant contributor to chronic migraine (CM). It is hypothesized that gene expression changes in peripheral blood cells can be used to detect the interaction of these influences. OBJECTIVE: Distinct genomic expression patterns for migraine and CM will be present. These genomic profiles will help clarify the interactions of inheritance and environment. This initial study begins to examine the feasibility of peripheral blood cell genomic analysis to assist in the understanding of the pathophysiology of migraine and CM. METHODS: Blood samples from patients were obtained either during an acute migraine or CM. Genomic expression patterns were analyzed using Affymetrix U95A microarrays. RESULTS: Expression patterns of 7 migraine and 15 CM patients were compared to four distinct control groups (total patients, n=56) including healthy subjects. A group of platelet genes were upregulated in both migraine and CM samples. Different gene expression patterns were also seen between migraine and CM. A group of immediate early genes including c-fos and cox-2 were expressed at higher levels in migraine, whereas specific mitochondrial genes were expressed at higher levels in CM. CONCLUSIONS: Increased expression of platelet genes in patients with migraine and CM suggests similar underlying pathophysiology. The differences seen between migraine and CM in other genes suggest an overlapping but not identical pathophysiology. Further genomic profiling studies will help define these relationships and provide further insights into headache pathogenesis.

Adolescent↗

Factors affecting the yield of pediatric EEGs in clinical practice.

Clinical factors affecting the yield of 2,500 pediatric electroencephalograms were analyzed. Electroencephalograms were interpreted as epileptiform in 40% of children with epilepsy. Most electroencephalograms were ordered for seizure in children not taking anti-epileptic drugs; just 15% showed epileptiform features. Six percent of electroencephalograms were epileptiform in non-seizure patients. The neurologist significantly influenced the odds of epileptiform interpretation (P = 0.022) and the recommendation to repeat the electroencephalogram (P < 0.001). In practice most electroencephalograms ordered for seizure are actually for non-seizure. In routine pediatric practice, electroencephalography has a low yield and appears to be over-used.

Adolescent↗