Parkinson's disease is caused by a progressive loss of the midbrain dopamine (DA) neurons in the substantia nigra pars compacta. Although the main cause of Parkinson's disease remains unknown, there is increasing evidence that it is a complex disorder caused by a combination of genetic and environmental factors, which affect key signalling pathways in substantia nigra DA neurons. Insights into pathogenesis of Parkinson's disease stem from in vitro and in vivo models and from postmortem analyses. Recent technological developments have added a new dimension to this research by determining gene expression profiles using high throughput microarray assays. However, many of the studies reported to date were based on whole midbrain dissections, which included cells other than DA neurons. Here, we have used laser microdissection to isolate single DA neurons from the substantia nigra pars compacta of controls and subjects with idiopathic Parkinson's disease matched for age and postmortem interval followed by microarrays to analyse gene expression profiling. Our data confirm a dysregulation of several functional groups of genes involved in the Parkinson's disease pathogenesis. In particular, we found prominent down-regulation of members of the PARK gene family and dysregulation of multiple genes associated with programmed cell death and survival. In addition, genes for neurotransmitter and ion channel receptors were also deregulated, supporting the view that alterations in electrical activity might influence DA neuron function. Our data provide a 'molecular fingerprint identity' of late-stage Parkinson's disease DA neurons that will advance our understanding of the molecular pathology of this disease.
individuals experience barriers to accessing many types of health care in the United States, resulting in substantial health care disparities. To improve health care in this patient population, it is important to recognize and study the potential factors limiting access to care. OBJECTIVE To examine deep brain stimulation (DBS) use in Parkinson disease (PD) to determine which factors, among a variety of demographic, clinical, and socioeconomic variables, drive DBS use in the United States. DESIGN, SETTING, AND PARTICIPANTS We queried the Nationwide Inpatient Sample in combination with neurologist and neurological surgeon countywide density data from the Area Resource File. We used International Classification of Diseases, Ninth Revision codes to identify discharges of patients at multicenter, all-payer, nonfederal hospitals in the United States diagnosed with PD (code 332.0) who were admitted for implantation of intracranial neurostimulator lead(s) (code 02.39), DBS. MAIN OUTCOMES AND MEASURES We analyzed factors predicting DBS use in PD using a hierarchical logistic regression analysis including patient and hospital characteristics. Patient characteristics included age, sex, comorbidity score, race, income quartile of zip code, and insurance type. Hospital characteristics included teaching status, size, regional location, urban vs rural setting, experience with DBS discharges, year, and countywide density of neurologists and neurological surgeons. RESULTS Query of the Nationwide Inpatient Sample yielded 2 408 302 PD discharges from 2002 to 2009; 18 312 of these discharges were for DBS. Notably, 4.7% of all PD discharges were African American, while only 0.1% of DBS for PD discharges were African American. A number of factors in the hierarchical multivariate analysis predicted DBS use including younger age, male sex, increasing income quartile of patient zip code, large hospitals, teaching hospitals, urban setting, hospitals with higher number of annual discharges for PD, and increased countywide density of neurologists (P < .05). Predictors of nonuse included African American race (P < .001), Medicaid use (P < .001), and increasing comorbidity score (P < .001). Countywide density of neurological surgeons and Hispanic ethnicity were not significant predictors. CONCLUSIONS AND RELEVANCE Despite the fact that African American patients are more often discharged from hospitals with characteristics predicting DBS use (ie, urban teaching hospitals in areas with a higher than average density of neurologists), these patients received disproportionately fewer DBS procedures compared with their non-African American counterparts. Increased reliance on Medicaid in the African American population may predispose to the DBS use disparity. Various other factors may be responsible, including disparities in access to care, cultural biases or beliefs, and/or socioeconomic status.
OBJECT The object of this study was to perform a systematic review, according to Preferred Reporting Items of Systematic reviews and Meta-Analyses (PRISMA) and Agency for Healthcare Research and Quality (AHRQ) guidelines, of the clinical efficacy and adverse effect profile of dorsal anterior cingulotomy compared with anterior capsulotomy for the treatment of severe, refractory obsessive-compulsive disorder (OCD). METHODS The authors included studies comparing objective clinical measures before and after cingulotomy or capsulotomy (surgical and radiosurgical) in patients with OCD. Only papers reporting the most current follow-up data for each group of investigators were included. Studies reporting results on patients undergoing one or more procedures other than cingulotomy or capsulotomy were excluded. Case reports and studies with a mean follow-up shorter than 12 months were excluded. Clinical response was defined in terms of a change in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score. The authors searched MEDLINE, PubMed, PsycINFO, Scopus, and Web of Knowledge through October 2013. English and non-English articles and abstracts were reviewed. RESULTS Ten studies involving 193 participants evaluated the length of follow-up, change in the Y-BOCS score, and postoperative adverse events (AEs) after cingulotomy (n = 2 studies, n = 81 participants) or capsulotomy (n = 8 studies, n = 112 participants). The average time to the last follow-up was 47 months for cingulotomy and 60 months for capsulotomy. The mean reduction in the Y-BOCS score at 12 months’ follow-up was 37% for cingulotomy and 55% for capsulotomy. At the last follow-up, the mean reduction in Y-BOCS score was 37% for cingulotomy and 57% for capsulotomy. The average full response rate to cingulotomy at the last follow-up was 41% (range 38%–47%, n = 2 studies, n = 51 participants), and to capsulotomy was 54% (range 37%–80%, n = 5 studies, n = 50 participants). The rate of transient AEs was 14.3% across cingulotomy studies (n = 116 procedures) and 56.2% across capsulotomy studies (n = 112 procedures). The rate of serious or permanent AEs was 5.2% across cingulotomy studies and 21.4% across capsulotomy studies. CONCLUSIONS This systematic review of the literature supports the efficacy of both dorsal anterior cingulotomy and anterior capsulotomy in this highly treatment-refractory population. The observational nature of available data limits the ability to directly compare these procedures. Controlled or head-to-head studies are necessary to identify differences in efficacy or AEs and may lead to the individualization of treatment recommendations.
Multiple barriers and facilitators affect weight management among at-risk families, which should be considered in future obesity interventions.
Background: Ommaya reservoirs are ventricular access devices used primarily for the administration of intrathecal antineoplastic chemotherapy. In patients with low or normal ventricular volume, stereotaxy can improve accuracy of catheter placement with minimal morbidity. Frameless stereotaxy has become an increasingly popular alternative to frame-based stereotaxy. Relative rates of successful catheter placement between these two techniques are not described in the literature. Objectives: To compare a large series of frameless to frame-based stereotactic catheter placements for Ommaya reservoirs, with an aim to compare accuracy and complication rate between the two procedures. Methods: A consecutive series of 41 frame-based and 68 frameless Ommaya reservoir placement procedures performed at our institution from 1998 to 2013 was reviewed. Patient demographics, operative accuracy and complication rates for the two techniques were compared. Results: Characteristics of the two groups were similar in diagnoses, age and other related factors. Comparison of frameless to frame-based stereotactic Ommaya catheter placement did not show significant differences in accuracy of placement, overall morbidity or mortality, or in any subcategory of complications. Conclusions: These findings suggest that frameless stereotactic Ommaya reservoir placement is as safe and accurate as the frame-based technique.
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