Patients with higher vitamin D levels show stronger improvement of self-reported depressive symptoms in psychogeriatric day-care setting.

Depression is a common psychiatric disorder among geriatric patients that decreases the quality of life and increases morbidity and mortality. Vitamin D as a neuro-steroid hormone might play a role in the onset and treatment of depression. In the present study, the association between depressive symptoms and vitamin D concentration in serum was evaluated. 140 patients of a psychogeriatric day-care unit were included. The geriatric depression scale (GDS) and the Hamilton depression rating scale (HDRS) were assessed at the beginning and end of treatment, GDS scores additionally 6 weeks after discharge from the day-care unit. Vitamin D levels were measured at the beginning of the treatment, routinely. Patients with levels below 30 µg/L were treated with 1000 IU vitamin D per day. There was no association between the severity of depressive symptoms and the concentration of vitamin D at the beginning of the treatment. Patients with higher vitamin D levels showed a stronger decline of depressive symptoms measured by the GDS during their stay in the day-care unit. We provide evidence that vitamin D serum levels might influence antidepressant therapy response in a geriatric population. Prospective studies are necessary to determine which patients may profit from add-on vitamin D therapy.

The Difficult Diagnosis of Posterior Cortical Atrophy in a 62-Year-Old Woman.

Posterior cortical atrophy (PCA) describes a rare heterogenous neurodegenerative syndrome with early visuospatial and visuoperceptual deficits due to atrophy of parieto-occipital brain regions. Here, we describe the case of a 62-year-old woman showing severe cognitive impairments as well as hemianopsia and all core symptoms of Bálint's syndrome. Years ago, the patient had complained about a "tunnel view" and concentration problems. The diagnostic results point to a case of PCA with underlying Alzheimer pathology. The disease course until diagnosis lasted for 7 years, reflecting the diagnostic difficulties with this still largely unknown syndrome. The unfamiliar symptom presentation including fluctuations in cognitive performance, affective symptoms, cerebrospinal fluid (CSF) biomarkers, which were at first inconspicuous, and a former suspected diagnosis of dissociative pseudodementia, altogether brought considerable uncertainty to the involved health-care professionals. We conclude that cases of "atypical dementia" presenting with visual symptoms, even if appearing unspecific at first, are suspect of PCA. This case report provides an ostensive overview of PCA, including imaging data, CSF-findings, original drawings and handwriting samples from the patient.

Video Monitoring for Fall Prevention and Patient Safety: Process Evaluation and Improvement.

BACKGROUND: Although video monitoring has been shown to reduce falls among at-risk hospitalized patients, there are no identified best practices for the monitoring process. PURPOSE: The purpose of this study was to evaluate the monitoring process at a large teaching hospital, with the goal of making improvements and standardizing monitoring practices. METHODS: Patients and nursing staff perceptions about the video monitoring process were elicited via survey, and perceptions of monitor technicians were obtained through structured interview. RESULTS: Video monitoring was perceived by all groups as effective in promoting patient safety. Nursing staff and monitor technicians also indicated that monitoring protects patient safety in other high-risk situations. Suggestions for improvement and standardization in the monitoring process were made by study participants. CONCLUSIONS: Suggested changes and standardization of the monitoring process have been implemented in the study facility. Insights are provided for other facilities considering video monitoring for patient safety.

Characterising HIV transmission risk among US patients with HIV in care: a cross-sectional study of sexual risk behaviour among individuals with viral load above 1500 copies/mL.

OBJECTIVES: Viral load and sexual risk behaviour contribute to HIV transmission risk. High HIV viral loads present greater transmission risk than transient viral 'blips' above an undetectable level. This paper therefore characterises sexual risk behaviour among patients with HIV in care with viral loads>1500 copies/mL and associated demographic characteristics. METHODS: This cross-sectional study was conducted at six HIV outpatient clinics in USA. The study sample comprises 1315 patients with HIV with a recent viral load >1500 copies/mL. This study sample was drawn from a larger sample of individuals with a recent viral load >1000 copies/mL who completed a computer-assisted self-interview (CASI) regarding sexual risk practices in the last 2 months. The study sample was 32% heterosexual men, 38% men who have sex with men (MSM) and 30% women. RESULTS: Ninety per cent of the sample had their viral load assay within 60 days of the CASI. Thirty-seven per cent reported being sexually active (vaginal or anal intercourse) in the last 2 months. Most of the sexually active participants reported always using condoms (56.9%) or limiting condomless sex to seroconcordant partners (serosorting; 29.2% overall and 42.9% among MSM). Among sexually active participants who reported condomless anal or vaginal sex with an at-risk partner (14%), most had viral loads>10 000 copies/mL (62%). CONCLUSIONS: A relatively small number of patients with HIV in care with viral loads above 1500 copies/mL reported concurrent sexual transmission risk behaviours. Most of the individuals in this small group had markedly elevated viral loads, increasing the probability of transmission. Directing interventions to patients in care with high viral loads and concurrent risk behaviour could strengthen HIV prevention and reduce HIV infections. TRIAL REGISTRATION NUMBER: NCT02044484, completed.

Evaluation of a computer-based and counseling support intervention to improve HIV patients' viral loads.

We sought to integrate a brief computer and counseling support intervention into the routine practices of HIV clinics and evaluate effects on patients' viral loads. The project targeted HIV patients in care whose viral loads exceeded 1000 copies/ml at the time of recruitment. Three HIV clinics initiated the intervention immediately, and three other HIV clinics delayed onset for 16 months and served as concurrent controls for evaluating outcomes. The intervention components included a brief computer-based intervention (CBI) focused on antiretroviral therapy adherence; health coaching from project counselors for participants whose viral loads did not improve after doing the CBI; and behavioral screening and palm cards with empowering messages available to all patients at intervention clinics regardless of viral load level. The analytic cohort included 982 patients at intervention clinics and 946 patients at control clinics. Viral loads were assessed at 270 days before recruitment, at time of recruitment, and +270 days later. Results indicated that both the control and intervention groups had significant reductions in viral load, ending with approximately the same viral level at +270 days. There was no evidence that the CBI or the targeted health coaching was responsible for the viral reduction in the intervention group. Results may stem partially from statistical regression to the mean in both groups. Also, clinical providers at control and intervention clinics may have taken action (e.g., conversations with patients, referrals to case managers, adherence counselors, mental health, substance use specialists) to help their patients reduce their viral loads. In conclusion, neither a brief computer-based nor targeted health coaching intervention reduced patients' viral loads beyond levels achieved with standard of care services available to patients at well-resourced HIV clinics.

Social and psychological correlates of unprotected anal intercourse among Hispanic-American women: implications for STI/HIV prevention.

Heterosexual anal intercourse is associated with increased risk for HIV and other sexually transmitted infections. Research on the social and psychological risk factors associated with heterosexual unprotected anal intercourse among Hispanic women in the USA is limited. We examined demographic, mental health, relationship power, sexual self-efficacy, self-esteem, acculturation and HIV knowledge as correlates of unprotected anal intercourse among 514 HIV-negative Hispanic women, 18 to 59 years of age, residing in one urban county in southern Florida. In both unadjusted and adjusted results, the likelihood of engaging in unprotected anal intercourse was associated with food insecurity in the past 30 days (adjusted odds ratio [AOR] = 1.57, 95% confidence interval [CI] 1.03, 2.40) and more interpersonal power attributed to the male partner (AOR = 1.63, 95%CI 1.08, 2.45). Not significant, yet of possible importance, were ever having engaged in exchange sex (AOR = 1.96, 95%CI = 0.97, 3.98) and lower HIV knowledge (AOR = 0.80, 95%CI = 0.63, 1.01). Interventions aimed at reducing heterosexual unprotected anal intercourse risk for HIV infection among Hispanic women may benefit by addressing socioeconomic and interpersonal issues, and assessing HIV knowledge and comprehension.

Astrocytic TDP-43 pathology in Alexander disease.

Alexander disease (AxD) is a rare neurodegenerative disorder characterized pathologically by the presence of eosinophilic inclusions known as Rosenthal fibers (RFs) within astrocytes, and is caused by dominant mutations in the coding region of the gene encoding glial fibrillary acidic protein (GFAP). GFAP is the major astrocytic intermediate filament, and in AxD patient brain tissue GFAP is a major component of RFs. TAR DNA binding protein of 43 kDa (TDP-43) is the major pathological protein in almost all cases of the neurodegenerative disease amyotrophic lateral sclerosis (ALS) and ∼50% of frontotemporal lobar degeneration (FTLD), designated as FTLD-TDP. In ALS and FTLD-TDP, TDP-43 becomes insoluble, ubiquitinated, and pathologically phosphorylated and accumulates in cytoplasmic inclusions in both neurons and glia of affected brain and spinal cord regions. Previously, TDP-43 was detected in RFs of human pilocytic astrocytomas; however, involvement of TDP-43 in AxD has not been determined. Here we show that TDP-43 is present in RFs in AxD patient brains, and that insoluble phosphorylated full-length and high molecular weight TDP-43 accumulates in white matter of such brains. Phosphorylated TDP-43 also accumulates in the detergent-insoluble fraction from affected brain regions of Gfap(R236H/+) knock-in mice, which harbor a GFAP mutation homologous to one that causes AxD in humans, and TDP-43 colocalizes with astrocytic RF pathology in Gfap(R236H/+) mice and transgenic mice overexpressing human wild-type GFAP. These findings suggest common pathogenic mechanisms in ALS, FTLD, and AxD, and this is the first report of TDP-43 involvement in a neurological disorder primarily affecting astrocytes.

Characteristics of African American Women and Their Partners With Perceived Concurrent Partnerships in 4 Rural Counties in the Southeastern U.S.

BACKGROUND: To the individual with concurrent partners, it is thought that having concurrent partnerships confers no greater risk of acquiring HIV than having multiple consecutive partnerships. However, an individual whose partner has concurrent partnerships (partner's concurrency) is at increased risk for incident HIV infection. We sought to better understand relationships characterized by partner's concurrency among African American women. METHODS: A total of 1013 African American women participated in a cross-sectional survey from 4 rural Southeastern counties. RESULTS: Older age at first sex was associated with lower prevalence of partner's concurrency (prevalence ratio, 0.70; 95% confidence interval, 0.57-0.87), but the participant's age was not associated with partner's concurrency. After adjusting for covariates, ever having experienced intimate partner violence (IPV) and forced sex were most strongly associated with partner's concurrency (prevalence ratios, 1.61 [95% confidence intervals, 1.23-2.11] and 1.65 [1.20-2.26], respectively). Women in mutually monogamous partnerships were the most likely to receive economic support from their partners; women whose partners had concurrent partnerships did not report more economic benefit than did those whose partners were monogamous. CONCLUSIONS: Associations between history of IPV and forced sex with partner's concurrency suggest that women with these experiences may particularly benefit from interventions to reduce partner's concurrency in addition to support for reducing IPV and other sexual risks. To inform these interventions, further research to understand partnerships characterized by partner's concurrency is warranted.

Relation of lead trajectory and electrode position to neuropsychological outcomes of subthalamic neurostimulation in Parkinson's disease: results from a randomized trial.

Deep brain stimulation of the subthalamic nucleus improves motor functions in patients suffering from advanced Parkinson's disease but in some patients, it is also associated with a mild decline in cognitive functioning about one standard deviation from the preoperative state. We assessed the impact of the cortical lead entry point, the subcortical electrode path and the position of the active electrode contacts on neuropsychological changes after subthalamic nucleus-deep brain stimulation compared to a control group of patients receiving best medical treatment. Sixty-eight patients with advanced Parkinson's disease were randomly assigned to have subthalamic nucleus-deep brain stimulation or best medical treatment for Parkinson's disease. All patients had a blinded standardized neuropsychological exam (Mattis Dementia Rating scale, backward digit span, verbal fluency and Stroop task performance) at baseline and after 6 months of treatment. Patients with subthalamic nucleus-deep brain stimulation were defined as impaired according to a mild decline of one or more standard deviations compared to patients in the best medical treatment group. The cortical entry point of the electrodes, the electrode trajectories and the position of the active electrode contact were transferred into a normalized brain volume by an automated, non-linear registration algorithm to allow accurate statistical group analysis using pre- and postoperative magnetic resonance imaging data. Data of 31 patients of the subthalamic nucleus-deep brain stimulation group and 31 patients of the best medical treatment group were analysed. The subthalamic nucleus-deep brain stimulation group showed impaired semantic fluency compared with the best medical treatment group 6 months after surgery (P = 0.02). Electrode trajectories intersecting with caudate nuclei increased the risk of a decline in global cognition and working memory performance. Statistically, for every 0.1 ml overlap with a caudate nucleus, the odds for a decline >1 standard deviation increased by a factor of 37.4 (odds ratio, confidence interval 2.1-371.8) for the Mattis Dementia Rating Scale and by a factor of 8.8 (odds ratio, confidence interval 1.0-70.9) for the backward digit span task. Patients with subthalamic nucleus-deep brain stimulation who declined in semantic verbal fluency, Stroop task and the backward digit span task performance showed a position of the active electrode outside the volume built by the active electrodes of stable performers. Passage of the chronic stimulation lead through the head of the caudate increases the risk of global cognitive decline and working memory performance after subthalamic nucleus-deep brain stimulation in Parkinson's disease. Therefore the electrode path should be planned outside the caudate nuclei, whenever possible. This study also stresses the importance of precise positioning of the active stimulating contact within the subthalamic volume to avoid adverse effects on semantic verbal fluency and response inhibition.

Cognitive disorders in advanced Parkinson's disease: challenges in the diagnosis of delirium.

Parkinson's disease (PD) is a neurodegenerative condition that is frequently associated with cognitive disorders. These can arise directly from the primary disease, or be triggered by external factors in susceptible individuals due to PD or other predisposing factors. The cognitive disorders encompass PD-associated cognitive impairment (PD-CI), delirium, PD treatment-associated cognitive side effects, cognitive non-motor fluctuations, and PD-associated psychosis. Accurate diagnosis of delirium is crucial because it often stems from an underlying disease that may be severe and require specific treatment. However, overlapping molecular mechanisms are thought to be involved in both delirium and PD, leading to similar clinical symptoms. Additionally, there is a bidirectional interaction between delirium and PD-CI, resulting in frequent concurrent processes that further complicate diagnosis. No reliable biomarker is currently available for delirium, and the diagnosis is primarily based on clinical criteria. However, the screening tools validated for diagnosing delirium in the general population have not been specifically validated for PD. Our review addresses the current challenges in the diagnosis of these cognitive disorders and highlights existing gaps within this field.

Beneficial effects of Nrf2 overexpression in a mouse model of Alexander disease.

Alexander disease is a fatal neurodegenerative disease caused by dominant mutations in glial fibrillary acidic protein (GFAP). The disease is characterized by protein inclusions called Rosenthal fibers within astrocyte cell bodies and processes, and an antioxidant response mediated by the transcription factor Nrf2. We sought to test whether further elevation of Nrf2 would be beneficial in a mouse model of Alexander disease. Forcing overexpression of Nrf2 in astrocytes of R236H GFAP mutant mice decreased GFAP protein in all brain regions examined (olfactory bulb, hippocampus, cerebral cortex, brainstem, cerebellum, and spinal cord) and decreased Rosenthal fibers in olfactory bulb, hippocampus, corpus callosum, and brainstem. Nrf2 overexpression also restored body weights of R236H mice to near wild-type levels. Nrf2 regulates several genes involved in homeostasis of the antioxidant molecule glutathione, and the neuroprotective effects of Nrf2 in other neurological disorders may reflect restoration of glutathione to normal levels. However, glutathione levels in R236H mice were not decreased. Nrf2 overexpression did not change glutathione levels or ratio of reduced to oxidized glutathione (indicative of oxidative stress) in olfactory bulb, where Nrf2 dramatically reduced GFAP. Depletion of glutathione through knock-out of the GCLM (glutamate-cysteine ligase modifier subunit) also did not affect GFAP levels or body weight of R236H mice. These data suggest that the beneficial effects of Nrf2 are not mediated through glutathione.

"A man's gonna do what a man wants to do": African American and Hispanic women's perceptions about heterosexual relationships: a qualitative study.

BACKGROUND: HIV prevention efforts have given limited attention to the relational schemas and scripts of adult heterosexual women. These broader schemas and scripts of romantic and other sexual liaisons, partner selection, relationship dynamics, and power negotiations may help to better understand facilitators and barriers to HIV risk-reduction practices. METHODS: We conducted exploratory qualitative interviews with 60 HIV-uninfected heterosexual African-American women from rural counties in North Carolina and Alabama, and Hispanic women from an urban county in southern Florida. Data were collected for relationship expectations; relationship experiences, and relationship power and decision-making. Interview transcripts underwent computer-assisted thematic analysis. RESULTS: Participants had a median age of 34 years (range 18-59), 34% were married or living as married, 39% earned an annual income of $12,000 or less, 12% held less than a high school education, and 54% were employed. Among the Hispanic women, 95% were foreign born. We identified two overarching relationship themes: contradictions between relationship expectations and desires and life circumstances that negated such ideals, and relationship challenges. Within the contradictions theme, we discovered six subthemes: a good man is hard to find; sex can be currency used to secure desired outcomes; compromises and allowances for cheating, irresponsible, and disrespectful behavior; redefining dating; sex just happens; needing relationship validation. The challenges theme centered on two subthemes: uncertainties and miscommunication, and relationship power negotiation. Gender differences in relationship intentions and desires as well as communication styles, the importance of emotional and financial support, and the potential for relationships to provide disappointment were present in all subthemes. In examining HIV risk perceptions, participants largely held that risk for HIV-infection and the need to take precautions were problems of women who differed from them (i.e., abuse drugs, are promiscuous, exchange sex). CONCLUSION: Underlying women's relational schemas was a belief that relationship priorities differed for men and women. Consequently, expectations and allowances for partner infidelity and negligent behaviors were incorporated into their scripts. Moreover, scripts endorsed women's use of sex as currency in relationship formation and endurance, and did not emphasize HIV risk. Both couple- and gender-specific group-level interventions are needed to deconstruct (breakdown) and reconstruct (rewrite) relationship scripts.

Feasibility of local field potential-guided programming for deep brain stimulation in Parkinson's disease: A comparison with clinical and neuro-imaging guided approaches in a randomized, controlled pilot trial.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for advanced Parkinson's disease (PD). Clinical outcomes after DBS can be limited by poor programming, which remains a clinically driven, lengthy and iterative process. Electrophysiological recordings in PD patients undergoing STN-DBS have shown an association between STN spectral power in the beta frequency band (beta power) and the severity of clinical symptoms. New commercially-available DBS devices now enable the recording of STN beta oscillations in chronically-implanted PD patients, thereby allowing investigation into the use of beta power as a biomarker for DBS programming. OBJECTIVE: To determine the potential advantages of beta-guided DBS programming over clinically and image-guided programming in terms of clinical efficacy and programming time. METHODS: We conducted a randomized, blinded, three-arm, crossover clinical trial in eight Parkinson's patients with STN-DBS who were evaluated three months after DBS surgery. We compared clinical efficacy and time required for each DBS programming paradigm, as well as DBS parameters and total energy delivered between the three strategies (beta-, clinically- and image-guided). RESULTS: All three programming methods showed similar clinical efficacy, but the time needed for programming was significantly shorter for beta- and image-guided programming compared to clinically-guided programming (p < 0.001). CONCLUSION: Beta-guided programming may be a useful and more efficient approach to DBS programming in Parkinson's patients with STN-DBS. It takes significantly less time to program than traditional clinically-based programming, while providing similar symptom control. In addition, it is readily available within the clinical DBS programmer, making it a valuable tool for improving current clinical practice.

Machine versus physician-based programming of deep brain stimulation in isolated dystonia: A feasibility study.

BACKGROUND: Deep brain stimulation of the internal globus pallidus effectively alleviates dystonia motor symptoms. However, delayed symptom control and a lack of therapeutic biomarkers and a single pallidal sweetspot region complicates optimal programming. Postoperative management is complex, typically requiring multiple, lengthy follow-ups with an experienced physician - an important barrier to widespread adoption in medication-refractory dystonia patients. OBJECTIVE: Here we prospectively tested the best machine-predicted programming settings in a dystonia cohort treated with GPi-DBS against the settings derived from clinical long-term care in a specialised DBS centre. METHODS: Previously, we reconstructed an anatomical map of motor improvement probability across the pallidal region using individual stimulation volumes and clinical outcomes in dystonia patients. We used this to develop an algorithm that tests in silico thousands of putative stimulation settings in de novo patients after reconstructing an individual, image-based anatomical model of electrode positions, and suggests stimulation parameters with the highest likelihood of optimal symptom control. To test real-life application, our prospective study compared results in 10 patients against programming settings derived from long-term care. RESULTS: In this cohort, dystonia symptom reduction was observed at 74.9 ± 15.3% with C-SURF programming as compared to 66.3 ± 16.3% with clinical programming (p < 0.012). The average total electrical energy delivered (TEED) was similar for both the clinical and C-SURF programming (262.0 µJ/s vs. 306.1 µJ/s respectively). CONCLUSION: Our findings highlight the clinical potential of machine-based programming in dystonia, which could markedly reduce the programming burden in postoperative management.

Is improvement in the quality of life after subthalamic nucleus stimulation in Parkinson's disease predictable?

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) significantly improves quality of life (QoL) in PD. However, QoL fails to improve in a relevant proportion of patients. We studied clinical baseline and progression parameters associated with improvement in QoL after DBS. Data from a German randomized, controlled study comparing DBS (60 patients) with best medical treatment (59 patients) were analyzed. Changes in patients' QoL were assessed using the Parkinson's Disease Questionnaire (PDQ-39) at baseline and at the 6-month follow-up. For the STN-DBS patients, the changes in PDQ-39 were correlated with predefined clinical preoperative and progression parameters. Scores for QoL improved after STN-DBS for 57% of the patients, and for 43% patients, they did not improve. Patients with improvement in QoL showed significantly higher cumulative daily "off" time. Changes in the PDQ-39 showed a significant positive correlation with the cumulative daily off time at baseline. Logistic regression analysis revealed that 1 additional hour off time at baseline increases the odds for improvement on PDQ-39 by a factor of 1.33 (odds ratio). In the postoperative course, changes in the PDQ-39 significantly correlated with the reduction of cumulative daily off time, an improvement on the UPDRS (UPDRS III off), and positive mood changes. Among the baseline parameters, the cumulative daily off time is the strongest predictor for improvement in disease-related QoL after DBS. Improvement in QoL after STN-DBS is also correlated with changes in motor functions and changes in depression and anxiety.

Presenting a successful stroke education model to meet the Joint Commission's Disease-Specific Care Certification.

Obtaining Joint Commission Disease-Specific Care Certification can be challenging for healthcare organizations. This article outlines the methodology for developing and implementing a comprehensive educational plan for a 560-bed academic teaching hospital. This information is valuable to any staff development educator who is leading the way to achieve Joint Commission Disease-Specific Care Certification.

Risk factors for executive dysfunction after subthalamic nucleus stimulation in Parkinson's disease.

A slight decline in cognitive functions and especially in executive functioning after deep brain stimulation (DBS) of the nucleus subthalamicus (STN) in patients with Parkinson's disease (PD) has been described. This study evaluated baseline parameters that contribute to a deterioration of cognitive functioning after DBS. We analyzed data from the neuropsychological protocol in a randomized controlled study comparing DBS with best medical treatment (BMT). Change scores were calculated for the cognitive domains "global cognitive functioning," "memory," "working memory," "attention," and "executive function." These domain-specific change scores were correlated with previously defined preoperative parameters. Compared with the BMT group (63 patients), the STN-DBS group (60 patients) showed a significant decline only in the domain executive function 6 months after DBS, which was significantly correlated with age, levodopa-equivalence dosage (LED) and axial subscore of the UPDRS in the off-medication state at baseline. Multiple regression analysis showed that these three factors explained, however, only about 23% of the variance. Patients with higher age, higher baseline LED, and/or higher axial subscore of the UPDRS at baseline have an increased risk for worsening of executive function after STN-DBS. High scores of these factors might reflect an advanced stage of disease progression. As these baseline factors explained the variance of the change score executive function only to a minor proportion, other factors including the surgical procedure, the exact placement of the electrode or postsurgical management might be more relevant for a decline in executive functioning after STN-DBS.

Minocycline 1-year therapy in multiple-system-atrophy: effect on clinical symptoms and [(11)C] (R)-PK11195 PET (MEMSA-trial).

The aim of the study was to investigate the efficacy of the antibiotic minocycline as a drug treatment in patients with Multiple-System-Atrophy Parkinson-type (MSA-P). Sixty-three patients were randomized to minocycline 200 mg/d (n = 32) or a matching placebo (n = 31). The primary outcome variable was the change in the value of the motor score of the Unified Multiple-System-Atrophy Rating-Scale (UMSARSII) from baseline to 48 weeks. Secondary outcome variables included subscores and individual Parkinsonian symptoms as determined by the UMSARS and the Unified-Parkinson's-Disease Rating-Scale (UPDRS). Health-related quality of life (HrQoL) was assessed using the EQ-5D and SF-12. "Progression rate" was assumed to be reflected in the change in motor function over 48 weeks. At 24 weeks and 48 weeks of follow-up, there was a significant deterioration in motor scores in both groups, but neither the change in UMSARSII nor in UPDRSIII differed significantly between treatment groups, i.e. "progression rate" was considered to be similar in both treatment arms. HrQoL did not differ among the two treatment arms. In a small subgroup of patients (n = 8; minocycline = 3, placebo = 5)[(11)C](R)-PK11195-PET was performed. The three patients in the minocycline group had an attenuated mean increase in microglial activation as compared to the placebo group (P = 0.07) and in two of them individually showed decreased [11C](R)-PK11195 binding actually decreased. These preliminary PET-data suggest that minocycline may interfere with microglial activation. The relevance of this observation requires further investigation. This prospective, 48 week, randomized, double-blind, multinational study failed to show a clinical effect of minocycline on symptom severity as assessed by clinical motor function.

Presentation, diagnosis, and management of multiple system atrophy in Europe: final analysis of the European multiple system atrophy registry.

Multiple system atrophy (MSA) is a Parkinson's Disease (PD)-like α-synucleinopathy clinically characterized by dysautonomia, parkinsonism, cerebellar ataxia, and pyramidal signs in any combination. We aimed to determine whether the clinical presentation of MSA as well as diagnostic and therapeutic strategies differ across Europe and Israel. In 19 European MSA Study Group centres all consecutive patients with a clinical diagnosis of MSA were recruited from 2001 to 2005. A standardized minimal data set was obtained from all patients. Four-hundred thirty-seven MSA patients from 19 centres in 10 countries were included. Mean age at onset was 57.8 years; mean disease duration at inclusion was 5.8 years. According to the consensus criteria 68% were classified as parkinsonian type (MSA-P) and 32% as cerebellar type (MSA-C) (probable MSA: 72%, possible MSA: 28%). Symptomatic dysautonomia was present in almost all patients, and urinary dysfunction (83%) more common than symptomatic orthostatic hypotension (75%). Cerebellar ataxia was present in 64%, and parkinsonism in 87%, of all cases. No significant differences in the clinical presentation were observed between the participating countries. In contrast, diagnostic work up and therapeutic strategies were heterogeneous. Less than a third of patients with documented orthostatic hypotension or neurogenic bladder disturbance were receiving treatment. This largest clinical series of MSA patients reported so far shows that the disease presents uniformly across Europe. The observed differences in diagnostic and therapeutic management including lack of therapy for dysautonomia emphasize the need for future guidelines in these areas.

Combined subthalamic and nucleus basalis of Meynert deep brain stimulation for Parkinson's disease with dementia (DEMPARK-DBS): protocol of a randomized, sham-controlled trial.

INTRODUCTION: Dementia in Parkinson's disease (PDD) is a common non-motor symptom of advanced disease, associated with pronounced neocortical cholinergic deficits due to neurodegeneration of the nucleus basalis of Meynert (NBM) and its cholinergic terminals. In advanced PD, patients often require advanced therapies such as infusion therapy or deep brain stimulation (DBS) to improve motor control. However, patients with associated dementia are commonly excluded from DBS because of potential deterioration of cognitive functions. Yet marked reductions in dopaminergic medication and the subsequent risk of side effects (e.g., cognitive decline, psychosis, delirium) suggest that critical re-consideration of DBS of the subthalamic nucleus (STN-DBS) for advanced stages of PD and PDD is worthwhile. In this Phase 1b study, we will provide STN-DBS to a cohort of PDD patients with severe motor fluctuations and combine two additional electrodes for augmentative neurostimulation of the NBM. METHODS: We aim to include 12 patients with mild-to-moderately severe PDD who fulfill indication criteria regarding motor symptoms for STN-DBS. Eligible patients will undergo implantation of a neurostimulation system with bilateral electrodes in both the STN and NBM. After 12 weeks of STN-DBS (visit 1/V1), participants will be randomized to receive either effective neurostimulation of the NBM (group 1) or sham stimulation of the NBM (group 2). NBM-DBS will be activated in all participants after 24 weeks of blinded treatment (visit 2/V2). The primary outcome will be the safety of combined bilateral STN- and NBM-DBS, determined by spontaneously-reported adverse events. Other outcome measures will comprise changes on scales evaluating cognition, activities of daily living functioning and clinical global impression, as well as motor functions, mood, behavior, caregiver burden and health economic aspects, and several domain-specific cognitive tests. Changes in scores (V1 - V2) for both treatment arms will undergo analysis of covariances, with baseline scores as covariates. PERSPECTIVE: The feasibility and safety of combined STN-NBM-DBS in patients with PDD will be assessed to determine whether additional NBM-DBS improves or slows the progression of cognitive decline. Positive results would provide a basic concept for future studies evaluating the efficacy of NBM-DBS in larger PDD cohorts. Indirectly, proof-of-safety of STN-DBS in PDD might influence patient selection for this standard treatment option in advanced PD. TRIAL REGISTRATION: ClinicalTrials.gov identifier (NCT number): NCT02589925.