Changes in CSF neurotransmitters in infantile spasms

Cerebrospinal fluid (CSF) from 7 patients with infantile spasms (mean age: 6.7 months) was collected before and after treatment with adrenocorticotropic hormone (ACTH). The concentration of neurotransmitter metabolites was analyzed using high-performance liquid chromatography and compared to the metabolite concentration in the CSF from 7 age-matched controls (mean age: 6.1 months). Pretreatment levels of CSF 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid, 3-methoxy-4-hydroxyphenyl glycol (MHPG), and kynurenine were significantly lower in infantile spasm patients compared to controls. Following treatment, marked increases in 5-HIAA and decreases in kynurenine levels were observed in the CSF of the 5 infants whose seizures were eliminated or reduced by ACTH. In the 2 nonresponders 5-HIAA levels decreased. The level of MHPG was reduced slightly in 5 infants, including the 2 nonresponders, and was increased in 2 responders. CSF homovanillic acid levels increased in 4 infantile spasm infants and decreased in 3 following ACTH. These data demonstrate that the presence of seizures in infantile spasms is associated with a significant decrease in serotonergic activity and that elimination of seizures by ACTH is accompanied by increased serotonin turnover. The simultaneous increase of 5-HIAA and decrease of kynurenine, an alternate metabolite of tryptophan, suggests an underlying disturbance of tryptophan metabolism in infantile spasms. The possibility that elimination of seizures by ACTH may be related to decreased production of certain kynurenine metabolites, particularly quinolinic acid, is discussed.     

An analysis of injury rates after the seasonal change in rugby league.

OBJECTIVES: To determine whether the increase in the incidence of injury found for the first summer season in which rugby league (RL) was played in the UK was repeated in subsequent summer seasons. DESIGN: A retrospective and prospective cohort study design. SETTING AND PARTICIPANTS: Injuries were recorded from all players who took part in 141 games over 3 summer seasons (1997 to 1999) for 1 professional team. These were compared against rates from previously collected data for 3 earlier winter and 1 summer season. ASSESSMENT OF RISK FACTORS: For each injury it was recorded in which season it occurred; how many games or training sessions, if any, were subsequently missed; the type, site and severity of injury. MAIN OUTCOME MEASURES: Injuries were reported as rate per 1000 hours, also broken down into severity according to the number of games missed and whether subsequent training sessions were missed. RESULTS: A sustained increase in injury incidence has been found comparing summer RL over RL played in the winter. There was an increase in injury rates for all sites and types, but not all reached significance. CONCLUSIONS: Data collected over 6 seasons indicate a higher risk of sustaining an injury playing summer RL, but the cause may be related to a combination of factors. These may include the ground or weather conditions associated with summer rugby, player characteristics or changes in the game itself and future research needs to investigate these further.     

Temporal concordance of anxiety disorders and child sexual abuse: implications for direct versus artifactual effects of sexual abuse.

This study examined the temporal concordance between the onset of childhood anxiety disorders and the points of onset and ending of child sexual abuse (CSA). Sexually abused children (N = 158) were assessed with structured diagnostic interviews. Onset ages for lifetime prevalence anxiety disorders were combined and sequenced with the onset and ending of sexual abuse. Hazard rates were calculated. Departures from the overall linear hazard trajectory for onsets were modeled using piecewise growth curve analyses. Increases from the overall trajectory were found around the point of sexual abuse onset for most childhood anxiety disorders. Decreases were found around the ending of sexual abuse. The risk for developing new anxiety disorders after the onset of sexual abuse showed a positive dose-effect relation with abuse severity. The findings add support to the idea that CSA can have a direct link to childhood anxiety disorders, apart from confounded vulnerability factors, postabuse events, or stable family background factors. The findings are contrasted with those from cross-sectional partial correlation studies that have suggested that there is little direct connection between sexual abuse and mental health outcomes.     

Sociotropy and Autonomy as Vulnerabilities to Specific Life Events: Issues in Life Event Categorization

This study examined the relations betweensociotropy, autonomy, and stress severity ratings forhypothetical life events that were objectivelycategorized as interpersonal or achievement-related infocus. The hypothesis that sociotropy and autonomyserve as vulnerability factors to dysphoria in thepresence of life stress that matches the theme of thevulnerability was also examined in 6-week and 12-week follow-up evaluations. Results provided onlypartial support for the predicted relations amongsociotropy, autonomy, and perceived stress severityratings of interpersonal and achievement-related events. Longitudinal results failed to support thehypothesis that sociotropy and autonomy serve asvulnerability factors for matching interpersonal andachievement-related stress. It was concluded thatobjectively categorizing life events as interpersonal orachievement-related is problematic given that themeaning of life events can vary across individuals, andthat these meanings are likely to vary partly as a function of sociotropy and autonomy.     

Total cortisol,free cortisol,and growth hormone associated with brief social separation experiences in young macaques

Many behavioral, immunological, and physiological consequences of brief maternal separation in bonnet (Macaca radiata) and pigtail monkeys (Macaca nemistrina) have been documented. However, the impact of social separation on plasma cortisol and growth hormone is unknown for these particular species. In the present study, the behavioral and endocrinological consequences of a 2-week maternal separation in socially housed infant bonnet and pigtail monkeys were followed. In seven pairs (separated and matched control) of bonnet and six pairs of pigtail infants, plasma was obtained under baseline, separated, and reunion conditions twice weekly for the duration of the study. Blood samples were obtained from both infants of the pair in approximately 10 min. Plasma total cortisol, free cortisol, and growth hormone were measured in these samples. Focal animal behavioral observations were made on all subjects twice daily throughout the study period. In both species, total cortisol and free cortisol rose immediately following maternal separation in comparison to the matched nonseparated controls and returned to basal levels (e.g., that of matched non-separted controls) following reunion with the mother. In contrast, plasma growth hormone rose only in the pigtail infants over a time course that peaked around the time of reunion. Multiple regression techniques indicated for the first week of separation, in the separated but not control subjects, that mean plasma free and total cortisol was positively related to distress behaviors (vocalization and postural slouch) observed during this week and negatively related to social behaviors (play and proximity to others) noted during the same period. In contrast, plasma growth hormone was related to both species and sex of the subjects but unrelated to behavioral variables. © 1995 John Wiley & Sons, Inc.     

Evidence of an abnormal intramuscular component of fatigue in multiple sclerosis

The goals of this study were to investigate muscle fatigue in patients with multiple sclerosis (MS), and to determine the relationships between muscle fatigue, clinical status, and perceived fatigue. The fatigability of the anterior tibial muscle was quantitated in patients and controls during 9 min of intermittent stimulation (used to eliminate central sources of muscle fatigue). During exercise, the decline in tetanic force, phosphocreatine, and intracellular pH was greater in patients than in controls. The compound muscle action potential amplitude did not decrease during exercise, indicating that there was no failure of neuromuscular transmission during fatigue. Thus, the excessive fatigue in MS developed from sources beyond the muscle membrane. Following exercise, the recovery of tetanic force was delayed in patients (a pattern that suggests abnormal excitation–contraction coupling), whereas the recovery of metabolites was complete in both groups. Muscular fatigue was correlated with clinical disability but not with perceived fatigue. These results suggests that fatigue in MS has both central (perception, upper motor neuron dysfunction) and peripheral (impaired metabolism and excitation–contraction coupling) components.© 1995 John Wiley &Sons, Inc.     

Analysis of the epsilon-sarcoglycan gene in familial and sporadic myoclonus-dystonia: evidence for genetic heterogeneity.

The epsilon-sarcoglycan gene (SGCE) on human chromosome 7q21 has been reported to be a major locus for inherited myoclonus-dystonia. Linkage to the SGCE locus has been detected in the majority of families tested, and mutations in the coding region have been found recently in families with autosomal dominant myoclonus-dystonia. To evaluate the relevance of SGCE in myoclonus-dystonia, we sequenced the entire coding region of the epsilon-sarcoglycan gene in 16 patients with either sporadic or familial myoclonus-dystonia. No mutations were found. This study suggests that epsilon-sarcoglycan does not play an important role in sporadic myoclonus-dystonia and supports genetic heterogeneity in familial cases.