Substantia Nigra Free Water Increases Longitudinally in Parkinson Disease.

BACKGROUND AND PURPOSE: Free water in the posterior substantia nigra obtained from a bi-tensor diffusion MR imaging model has been shown to significantly increase over 1- and 4-year periods in patients with early-stage idiopathic Parkinson disease compared with healthy controls, which suggests that posterior substantia nigra free water may be an idiopathic Parkinson disease progression biomarker. Due to the known temporal posterior-to-anterior substantia nigra degeneration in idiopathic Parkinson disease, we assessed longitudinal changes in free water in both the posterior and anterior substantia nigra in patients with later-stage idiopathic Parkinson disease and age-matched healthy controls for comparison. MATERIALS AND METHODS: Nineteen subjects with idiopathic Parkinson disease and 19 age-matched healthy control subjects were assessed on the same 3T MR imaging scanner at baseline and after approximately 3 years. RESULTS: Baseline mean idiopathic Parkinson disease duration was 7.1 years. Both anterior and posterior substantia nigra free water showed significant intergroup differences at baseline (P < .001 and P = .014, respectively, idiopathic Parkinson disease versus healthy controls); however, only anterior substantia nigra free water showed significant longitudinal group × time interaction increases (P = .021, idiopathic Parkinson disease versus healthy controls). There were no significant longitudinal group × time interaction differences found for conventional diffusion tensor imaging or free water-corrected DTI assessments in either the anterior or posterior substantia nigra. CONCLUSIONS: Results from this study provide further evidence supporting substantia nigra free water as a promising disease-progression biomarker in idiopathic Parkinson disease that may help to identify disease-modifying therapies if used in future clinical trials. Our novel finding of longitudinal increases in anterior but not posterior substantia nigra free water is potentially a result of the much longer disease duration of our cohort compared with previously studied cohorts and the known posterior-to-anterior substantia nigra degeneration that occurs over time in idiopathic Parkinson disease.

Influence of gender on Tourette syndrome beyond adolescence.

Although boys are disproportionately affected by tics in Tourette syndrome (TS), this gender bias is attenuated in adulthood and a recent study has suggested that women may experience greater functional interference from tics than men. The authors assessed the gender distribution of adults in a tertiary University-based TS clinic population and the relative influence of gender and other variables on adult tic severity (YGTSS score) and psychosocial functioning (GAF score). We also determined retrospectively the influence of gender on change in global tic severity and overall TS impairment (YGTSS) since adolescence. Females were over-represented in relation to previously published epidemiologic surveys of both TS children and adults. Female gender was associated with a greater likelihood of tic worsening as opposed to tic improvement in adulthood; a greater likelihood of expansion as opposed to contraction of motor tic distribution; and with increased current motor tic severity and tic-related impairment. However, gender explained only a small percentage of the variance of the YGTSS global severity score and none of the variance of the GAF scale score. Psychosocial functioning was influenced most strongly by tic severity but also by a variety of comorbid neuropsychiatric disorders.

Phase white matter signal abnormalities in patients with clinically isolated syndrome and other neurologic disorders.

BACKGROUND AND PURPOSE: Identifying MRI biomarkers that can differentiate multiple sclerosis patients from other neurological disorders is a subject of intense research. Our aim was to investigate phase WM signal abnormalities for their presence, prevalence, location, and diagnostic value among patients with clinically isolated syndrome and other neurologic disorders and age-, sex-, and group-matched healthy controls. MATERIALS AND METHODS: Forty-eight patients with clinically isolated syndrome and 30 patients with other neurologic diseases and a healthy control group (n = 47) were included in the study. Subjects were scanned at 3T by using SWI-filtered phase and T2WI, with WM signal abnormalities ≥3 mm being classified. RESULTS: Patients with clinically isolated syndrome had significantly more phase and T2 WM signal abnormalities than healthy controls (P < .001). Phase WM signal abnormalities were more prevalent among patients with clinically isolated syndrome compared with patients with other neurologic disorders (4:1 ratio), whereas T2 WM signal abnormalities were more ubiquitous with a 2:1 ratio. The presence of phase WM signal abnormalities was sensitive for clinically isolated syndrome (70.8%) and achieved a moderate-to-high specificity for differentiating patients with clinically isolated syndrome and healthy controls, patients with other neurologic disorders, and patients with other neurologic disorders of other autoimmune origin (specificity, 70%-76.7%). Combining the presence of ≥2 phase lesions with the McDonald 2005 and 2010 criteria for dissemination in space improved the specificity (90%), but not the accuracy, in differentiating patients with clinically isolated syndrome from those with other neurologic disorders. In subanalyses among patients with clinically isolated syndrome who converted to clinically definite multiple sclerosis versus those who did not within a 3-year follow-up period, converters had significantly more phase (P = .008) but not T2 or T1 WM signal abnormalities. CONCLUSIONS: Phase WM signal abnormalities are prevalent among patients with clinically isolated syndrome. The presence of (multiple) phase WM signal abnormalities tended to be more predictive of conversion to clinically definite multiple sclerosis and was specific in differentiating patients with clinically isolated syndrome and other neurologic disorders, compared with T2 WM signal abnormalities; however, the accuracy remains similar to that of the current McDonald criteria.

Parkinson's disease: a preliminary study of yohimbine challenge in patients with anxiety.

In this pilot study, we performed an oral yohimbine challenge in 6 patients with Parkinson's disease (PD) and anxiety or depression, 2 parkinsonian patients without psychiatric illness, and 2 healthy control subjects to determine whether patients with Parkinson's disease and anxiety respond to this adrenergic agent in the same way patients with idiopathic anxiety disorders respond. Given the atypical nature of depression in Parkinson's disease (characterized by prominent anxiety), we also wanted to see if patients with Parkinson's disease and depression (but no history of anxiety) are susceptible to yohimbine-induced panic. Parkinsonian patients with anxiety developed panic attacks at frequencies comparable to primary psychiatric patients with panic disorder. The one patient with PD and a history of major depression alone developed a panic attack. Regardless of their history of anxiety or depression, parkinsonian patients demonstrated a vulnerability to yohimbine-induced somatic symptoms.

Life course transitions of American children: parental cohabitation, marriage, and single motherhood.

We examine the life course transitions into and from families headed by unmarried cohabiting couples for a recent cohort of American children. Life table estimates, based on data from the National Longitudinal Survey of Youth mother-child files, indicate about one in four children will live in a family headed by a cohabiting couple sometime during childhood. Economic uncertainty is an important factor determining whether children in single-parent families subsequently share a residence with a mother's unmarried partner. Moreover, virtually all children in cohabiting-couple families will experience rapid subsequent changes in family status. Our estimates provide a point of departure for future work on children's exposure to parental cohabitation and its social and economic implications.

Influence of family history on clinical expression of Tourette's syndrome.

OBJECTIVE: To determine the influence of family history on clinical expression of Tourette's syndrome (TS). BACKGROUND: Recent studies have suggested that clinical expression of TS is similar among sporadic (SP) and familial patients but may be influenced by bilineal (BIL) transmission of tics or obsessive-compulsive behavior (OCB) in high-density pedigrees. METHODS: The authors used family history methodology, supported by direct examination of affected relatives in 73% of familial patients, to determine the frequency of SP TS, and of unilineal (UNL) and BIL transmission of tics or OCB in 111 consecutively ascertained juvenile TS patients. For individuals in each group, severity of tics, attention deficit hyperactivity disorder (ADHD), and OCB were assessed at presentation and after a mean follow-up interval of 2.6 years, using the Tourette's Syndrome Global Scale and the Clinical Global Impression scales. The phenomenology of OCB was evaluated using the symptom checklist of the Children's Yale-Brown Obsessive Compulsive Scale. RESULTS: The authors documented BIL transmission of tics in seven patients (6%). Patient age and sex were similar for the SP (n = 21; 19%), UNL (n = 66; 59%), and BIL (n = 24; 22%) groups, as was ADHD and tic severity at presentation and follow-up. Severity of OCB differed significantly between groups, with moderate to severe OCB affecting 5% of SP, 12% of UNL, and 37% of BIL patients at presentation (p = 0.007), and 5% of SP, 17% of UNL, and 54% of BIL patients at follow-up (p = 0.0001). Relative to UNL or SP patients, BIL patients were more likely to exhibit self-injurious behaviors (p = 0.0005). CONCLUSIONS: OCB is less prominent in SP than in familial TS, perhaps reflecting a more restricted pathophysiology in this subgroup. Although BIL transmission of tics is relatively infrequent in consecutive TS pedigrees, cotransmission of OCB from an otherwise unaffected parent is common and significantly influences development of OCB and self-injurious behaviors, but not tics, in offspring. Genetic heterogeneity, epigenetic factors, and gene-environment interactions may play a more important role than genetic dosage effects in determining tic severity in TS.

State abortion policy, geographic access to abortion providers and changing family formation.

CONTEXT: One of the goals in cutting welfare payments and setting time limits on welfare receipt is the reduction of out-of-wedlock childbearing among poor women. Yet such changes may increase the demand for abortion at the same time that access to abortion has decreased, throwing into doubt the potential effect of these changes on the proportion of women who are heading families. METHODS: State and county fixed-effects models were used to estimate the effects of factors influencing abortion availability--geographic access, parental notification requirements and Medicaid funding restrictions--on the county-level proportion of women heading households. RESULTS: The decline in geographic access to abortion providers during the 1980s accounted for a small but significant portion of the rise in the percentage of women heading families (about 2%). Restrictions on Medicaid funding for abortion accounted for about half of the increase in female headship among blacks, while new state parental notification requirements contributed modestly to the rise in the proportion of white women heading single-parent families. CONCLUSIONS: Welfare reform legislation and attempts to reduce the availability of abortion services in the United States appear to be working at cross-purposes. Cutbacks in access to abortion may have contributed modestly to the increase in the proportion of women heading households.

PIP: This study examined whether new barriers to abortion access are likely to contribute to increased female headship in the US. State and country fixed effects models are estimated for the impact of geographic access to abortion providers, notification requirements, parental consent, and Medicaid funding restrictions. Data were obtained from county records from summary tape files of the 1980 and 1990 censuses; abortion provider information from the Alan Guttmacher Institute; and physicians active in OB-GYN patient care data from the Bureau of Health Professionals Area Resource File. Pooled data amounted to 6132 observations for 3066 counties. The data included nonmarital births without a marriage and marital births followed by separation or divorce. Sensitivity analysis accounted for local divorce rates. Fixed effects controls accounted for unobserved variables. Population-weighted descriptive statistics are provided for dependent and key independent variables. Abortion provider declines ranged from 13% to 19%. Findings indicate that declines in geographic access accounted for a small, but significant, decline in increased female headship. About 50% of the increase among Black female headship was accounted for by restrictions on Medicaid funding. A modest amount of the rise in White female headship was due to state parent notification requirements. The difference in the estimated impact of abortion providers in the state and county specific models supported findings of Kane and Staiger. Sensitivity models did not alter the effects of access to abortion providers and physicians. Findings suggest conflicting or competing public policy goals.

Slowed reaction time during a continuous performance test in children with Tourette's syndrome.

The phenomonology of Tourette's syndrome (TS) not only includes tics but also apparent deficits in attention. These attentional deficits in TS likely involve anomalies in frontal-striatal circuits. In this study, performance of 22 boys with TS and 22 age-matched boys without TS was compared on a continuous performance test (CPT) of attention. TS children demonstrated a normal capacity for discriminating targets from nontargets during the task, but showed significantly slower reaction times than controls. Severity of complex vocal tics was predictive of reaction time performance. Possible explanations for these findings are discussed and include the presence of attentional difficulties in TS, interference associated with tic suppression, a conservative strategy taken by TS children, and a general impairment of motor performance.

Predictors of clonidine response in Tourette syndrome: implications and inferences.

Clonidine is an alpha-adrenergic agonist which may alleviate emerging symptoms in Tourette syndrome, an observation that has fueled speculation regarding involvement of stress-sensitive central noradrenergic systems in this disorder. We conducted a retrospective study of 53 juvenile patients with Tourette syndrome to assess predictors of short-term behavioral and tic response to oral clonidine and to examine the relationship, if any, among pretreatment blood pressure, tic severity, and clonidine response. When adverse effects were considered, older subjects experienced a better therapeutic response to clonidine, independent of dose. Improvement in symptoms of attention-deficit hyperactivity disorder was associated with a longer duration of vocal tics before treatment. Baseline sitting diastolic blood pressure was directly correlated with measures of tic severity but not with tic response to clonidine. The findings (1) provide indirect support for involvement of central noradrenergic systems in tic expression; (2) suggest that emergence of a tic-related neurophysiologic dysfunction may be necessary for optimal behavioral response to clonidine in Tourette syndrome; and (3) provide broad guidelines for the clinician considering clonidine therapy for pediatric patients with Tourette syndrome, particularly those with comorbid attention-deficit hyperactivity disorder.

Parkinsonism associated with fluoxetine and cimetidine: a case report.

Fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) are effective for the treatment of depression in the elderly and offer a safer side-effect profile as compared to tricyclics and monoamine oxidase inhibitors. We report a case in which a patient treated with fluoxetine developed parkinsonism following the introduction of cimetidine. Inhibition of hepatic P450 cytochrome enzymes by cimetidine with an increase in serum levels of norfluoxetine may have precipitated this extrapyramidal syndrome, which has been related to agonism of the serotonergic input to nigrostriatal tracts and basal ganglia. Parkinsonism as a side effect of SSRIs occurs infrequently, suggesting an idiosyncratic response resulting from a functional imbalance of serotonergic and dopaminergic activity in susceptible individuals. Careful monitoring of geriatric patients treated with fluoxetine is indicated, particularly for those on high doses, those with impaired hepatic functioning, or those treated with concurrent medications that slow the metabolism of fluoxetine.

Clinical evidence of genomic imprinting in Tourette's syndrome.

Recent genetic studies of Tourette's syndrome (TS) have suggested a sex-specific expression of TS behaviors but not a sex-associated difference in their transmission. In a retrospective study designed to assess the influence of gender of the affected parent on childhood TS phenotype, we compared unmedicated TS subjects with patrilineal (n = 25) or matrilineal (n = 25) inheritance of TS, as determined by family history methodology, with respect to demographic variables, temporal profile of tic evolution, and clinical ratings of tics and associated behaviors, particularly obsessive-compulsive symptoms and attention deficit hyperactivity disorder (ADHD). Maternal transmission of TS was characterized by trends toward greater motor tic complexity and more frequent noninterfering rituals (p < 0.05); paternal transmission was associated with increased vocal tic frequency (p = 0.01), an earlier onset of vocal tics relative to motor tics (p < 0.01), and more prominent ADHD behaviors, including motor restlessness (p < 0.01). These findings are consistent with genomic imprinting in TS. Confirmation of this phenomenon promises not only to advance understanding concerning the genetic link between TS and ADHD but may also help to explain the apparent fit of competing models of genetic transmission in TS.

[Living arrangements and economic well-being of American children]. / Environnement familial et bien-etre economique des enfants americains.

"The objective of this paper is to evaluate the extent to which racial variation in children's economic well-being resides in divergent parental work patterns and/or family living arrangements. This is accomplished using recently-released data from the 1 percent sample of the Public Use Microdata Sample of the 1990 [U.S.] decennial census. The results indicate that racial differences in family structure undermine efforts to eliminate racial inequality among American children. Among blacks, for example, the high proportions of children living in female-headed families account for 60 percent of the difference from white children in poverty rates. Similarly, racial differences in parental work patterns contribute to (but cannot explain completely) racial variation in child poverty. Among black children in married-couple families, poverty rates are roughly twice those of their white counterparts, even though black children are more likely to have both parents working." (SUMMARY IN ENG AND SPA)

Health and well-being among rural Americans: variations across the life course.

This study uses data from the 1988 National Survey of Families and Households conducted by the University of Wisconsin to examine spatial variations in physical, mental, and social well-being among young, middle aged, and elderly American adults. Rural residents of all ages were found to consistently rate their physical health more poorly than nonrural residents. Both young and old rural adults also rated themselves less happy than nonrural residents. However, middle-aged and elderly rural residents appear better off on the majority of six other indicators of well-being, and this group reports the highest proportion of adults with no health impairments. Finally, rural residents of all ages possess distinct advantages in terms of several measures of social ties.

Tremor at onset. Predictor of cognitive and motor outcome in Parkinson's disease?

We examined 46 male patients with idiopathic Parkinson's disease to see whether tremor at onset was as useful a predictor of benign clinical outcome as tremor predominance after several years. When we compared patients with tremor at onset (n = 27) with those whose disease began with brady-kinesia/rigidity (n = 9), or gait disorder (n = 10), we found no significant differences after a mean of 7 years in motor, cognitive, or affective status. Sixteen of the tremor-onset patients continued to have tremor predominance with minimal gait disorder after about 7 years. These tremor-predominant patients had significantly better motor outcome and somewhat better cognitive outcome than either tremor-onset patients who subsequently developed gait disorder (n = 11) or patients without tremor at onset (n = 19). Tremor predominance after several years appears to be a better predictor of a benign clinical course of Parkinson's disease than tremor at onset.

Carbamazepine-induced tics.

Although a variety of dyskinesias are known to develop during anticonvulsant therapy, carbamazepine-induced tics are rarely recognized. We report three patients with an underlying movement disorder (Huntington's disease, tardive dyskinesia, and Tourette's syndrome) who experienced the onset or exacerbation of tics after the introduction of carbamazepine. These cases confirm the phenomenon of carbamazepine-induced tics and suggest that basal ganglia neuropathology may be an important predisposing factor. The dopaminergic effects of carbamazepine may be responsible for the induction of tics.

Sensory tics in Tourette's syndrome.

Sensory tics are localized uncomfortable sensations for which patients attempt to obtain relief by producing movements or vocalizations. We report 3 patients with Tourette's syndrome (TS) and sensory tics to illustrate this poorly recognized symptom. A survey of 34 randomly selected TS patients indicates that sensory tics are common and should be considered part of a clinical spectrum of tics and associated sensory phenomena.

The underemployment of American rural women: prevalence, trends and spatial inequality.

PIP: The growing numerical significance of women in the US nonmetropolitan labor force has not been matched by parallel efforts to document the changing quality of their employment. In this paper. Lichter uses the labor utilization framework of Clogg and Sullivan to examine the prevalence and spatial convergence of various forms of female underemployment during 1970-1985. Data from the March annual demographic files of the Current Population Survey reveal that underemployment has been a significant aspect of the employment experiences of nonmetropolitan women during this period. There has been little evidence of spatial or sex convergence in labor market outcomes. Roughly 1 of every 3 rural female workers today is a discouraged worker, jobless, employed part-time involuntarily, or working for poverty-level wages. Moreover, rural women continue to suffer substantially higher levels of economic underemployment than urban women and rural men. This study reinforces the view that rural women remain a seriously underutilized labor resource in the US.^ieng