IgA-Biome Profiles Correlate with Clinical Parkinson's Disease Subtypes.

BACKGROUND: Parkinson's disease is a heterogeneous neurodegenerative disorder with distinctive gut microbiome patterns suggesting that interventions targeting the gut microbiota may prevent, slow, or reverse disease progression and severity. OBJECTIVE: Because secretory IgA (SIgA) plays a key role in shaping the gut microbiota, characterization of the IgA-Biome of individuals classified into either the akinetic rigid (AR) or tremor dominant (TD) Parkinson's disease clinical subtypes was used to further define taxa unique to these distinct clinical phenotypes. METHODS: Flow cytometry was used to separate IgA-coated and -uncoated bacteria from stool samples obtained from AR and TD patients followed by amplification and sequencing of the V4 region of the 16 S rDNA gene on the MiSeq platform (Illumina). RESULTS: IgA-Biome analyses identified significant alpha and beta diversity differences between the Parkinson's disease phenotypes and the Firmicutes/Bacteroides ratio was significantly higher in those with TD compared to those with AR. In addition, discriminant taxa analyses identified a more pro-inflammatory bacterial profile in the IgA+ fraction of those with the AR clinical subclass compared to IgA-Biome analyses of those with the TD subclass and with the taxa identified in the unsorted control samples. CONCLUSION: IgA-Biome analyses underscores the importance of the host immune response in shaping the gut microbiome potentially affecting disease progression and presentation. In the present study, IgA-Biome analyses identified a unique proinflammatory microbial signature in the IgA+ fraction of those with AR that would have otherwise been undetected using conventional microbiome analysis approaches.

Fecal microbiota transplantation in Parkinson's disease-A randomized repeat-dose, placebo-controlled clinical pilot study.

Background and purpose: The intestinal microbiome plays a primary role in the pathogenesis of neurodegenerative disorders and may provide an opportunity for disease modification. We performed a pilot clinical study looking at the safety of fecal microbiota transplantation (FMT), its effect on the microbiome, and improvement of symptoms in Parkinson's disease. Methods: This was a randomized, double-blind placebo-controlled pilot study, wherein orally administered lyophilized FMT product or matching placebo was given to 12 subjects with mild to moderate Parkinson's disease with constipation twice weekly for 12 weeks. Subjects were followed for safety and clinical improvement for 9 additional months (total study duration 12 months). Results: Fecal microbiota transplantation caused non-severe transient upper gastrointestinal symptoms. One subject receiving FMT was diagnosed with unrelated metastatic cancer and was removed from the trial. Beta diversity (taxa) of the microbiome, was similar comparing placebo and FMT groups at baseline, however, for subjects randomized to FMT, it increased significantly at 6 weeks (p = 0.008) and 13 weeks (p = 0.0008). After treatment with FMT, proportions of selective families within the phylum Firmicutes increased significantly, while proportion of microbiota belonging to Proteobacteria were significantly reduced. Objective motor findings showed only temporary improvement while subjective symptom improvements were reported compared to baseline in the group receiving FMT. Constipation, gut transient times (NS), and gut motility index (p = 0.0374) were improved in the FMT group. Conclusions: Subjects with Parkinson's disease tolerated multi-dose-FMT, and experienced increased diversity of the intestinal microbiome that was associated with reduction in constipation and improved gut transit and intestinal motility. Fecal microbiota transplantation administration improved subjective motor and non-motor symptoms. Clinical trial registration: ClinicalTrial.gov, identifier: NCT03671785.

Aggression Prevention Training for Individuals With Dementia and Their Caregivers: A Randomized Controlled Trial.

OBJECTIVE: International appeals call for interventions to prevent aggression and other behavioral problems in individuals with dementia (IWD). Aggression Prevention Training (APT), based on intervening in three contributors to development of aggression (IWD pain, IWD depression, and caregiver-IWD relationship problems) aims to reduce incidence of aggression in IWD over 1 year. DESIGN: Randomized, controlled trial. SETTING: Three clinics that assess, diagnose, and treat dementia. PARTICIPANTS: Two hundred twenty-eight caregiver-IWD dyads who screened positive for IWD pain, IWD depression, or caregiver-IWD relationship problems randomized to APT or Enhanced Usual Primary Care (EU-PC). INTERVENTION: APT, a skills-based intervention delivered over 3 months to address pain/depression/caregiver-IWD relationship issues. EU-PC included printed material on dementia and community resources; and eight brief, weekly support calls. MEASUREMENTS: The primary outcome was incidence of aggression over 1 year, determined by the Cohen Mansfield Agitation Inventory-Aggression Subscale. Secondary outcomes included pain, depression, caregiver-IWD relationship, caregiver burden, positive caregiving, behavior problems, and anxiety. RESULTS: Aggression incidence and secondary outcomes did not differ between groups. However, in those screening positive for IWD depression or caregiver-IWD relationship problems, those receiving EU-PC had significant increases in depression and significant decreases in quality of the caregiver-IWD relationship, whereas those receiving APT showed no changes in these outcomes over time. CONCLUSION: The cost to patients, family, and society of behavioral problems in IWD, along with modest efficacy of most pharmacologic and nonpharmacologic interventions, calls for more study of novel preventive approaches.

Longitudinal feasibility of MINDSET: a clinic decision aid for epilepsy self-management.

The purpose of this paper is to report on the development and feasibility of the longitudinal version of MINDSET, a clinical tool to assist patients and health-care providers in epilepsy self-management. A previous study described the feasibility of using MINDSET to identify and prioritize self-management issues during a clinic visit. This paper describes the development of the longitudinal version of MINDSET and feasibility test over multiple visits with a printed action plan for goal setting and the capacity for monitoring changes in self-management. Feasibility was assessed based on 1) postvisit patient and provider interviews addressing ease of use and usefulness, patient/provider communication, and shared decision-making and 2) the capacity of the tool to monitor epilepsy characteristics and self-management over time. Results indicate MINDSET feasibility for 1) identifying and facilitating discussion of self-management issues during clinic visits, 2) providing a printable list of prioritized issues and tailored self-management goals, and 3) tracking changes in epilepsy characteristics and self-management over time.

Adult moyamoya disease in an urban center in the United States is associated with a high burden of watershed ischemia.

BACKGROUND: Adult moyamoya disease is rare in the United States, and patients mostly present with cerebral ischemia. However, clinical and neurodiagnostic correlates of ischemia are not well known in this population. We sought to characterize the clinical and radiographic features of moyamoya disease in a large urban center in the United States, with a focus on angiographic and neuroimaging patterns of ischemia. METHODS AND RESULTS: We retrospectively reviewed charts of consecutive adult moyamoya disease patients evaluated at 2 centers in Houston, Texas from January 2002 to December 2011. We reviewed all available cerebral angiograms and neuroimaging studies to evaluate the Suzuki grades, presence of intracranial hemorrhage or ischemia, infarct patterns, and vascular territory distribution. Our analysis was mainly descriptive. We identified 31 adults with moyamoya disease who met our inclusion criteria. The female-to-male ratio was 2.4:1. The majority of patients were white, followed by Hispanic, black, and Asian. Most presented with ischemia (61%), followed by headaches, and intracranial hemorrhage. Of the 22 patients with available neuroimaging, 72.7% had ischemic findings, with the vast majority having a watershed pattern (81.3%). CONCLUSIONS: We observed a high burden of ischemia, mostly watershed pattern on neuroimaging in our adult moyamoya disease patients. Long-term monitoring of adult moyamoya disease patients in the United States would be useful to better understand the natural history of this condition.

Socioeconomic status, health care use, and outcomes: persistence of disparities over time.

PURPOSE: To determine the persistence of disparities in health care use and outcomes in socioeconomically diverse populations of epilepsy patients. METHODS: We followed patients for a year at one clinic in Houston and two in New York City that serve predominantly low-income, minority, Medicaid-insured, or uninsured patients, and a fourth clinic in Houston that serves a more balanced racial/ethnic and higher socioeconomic status (SES) population. We interviewed the patients several times regarding health care use, seizures, side effects, and outcomes, and examined differences between the patients at the three low-SES clinics and the patients at the high-SES clinic. KEY FINDINGS: After controlling for patients' age, gender, race/ethnicity, marital status, seizures, and side effects we found that low SES patients had consistently higher use of the hospital emergency room and more visits to a general practitioner. Hospitalizations were also consistently higher but the differences were not significant in most periods. Neurologist visits were relatively similar. Patients at the low SES sites also had a greater likelihood of having uncontrolled seizures, drug-related side effects, to be stigmatized, and have a lower overall quality of life throughout the study period. SIGNIFICANCE: These findings suggest the persistence of SES-related disparities in health care use and outcomes among patients with epilepsy who are receiving regular care.

Unilateral opercular lesion and eating-induced seizures.

Eating-induced seizures are an uncommon presentation of reflex epilepsy, a condition characterized by seizures provoked by specific stimuli. Most reports have identified aetiology associated with malformations of cortical developmental, hypoxic brain injury, previous meningoencephalitis or static encephalopathy. We present a patient with eating-induced reflex seizures, which began several years after treatment for an opercular primitive neuroectodermal tumour (PNET), and who subsequently underwent in-depth clinical and video-EEG analysis for her seizures. This patient noted rapid improvement with decreased frequency of seizure activity after treatment with valproic acid. We discuss the aetiology of reflex epilepsy, the anatomical basis of eating-induced epilepsy, and review the current literature.

Socioeconomic status and self-management in epilepsy: comparison of diverse clinical populations in Houston, Texas.

We compared the scores on self-management and associated psychosocial scales of patients with epilepsy at two clinics in Houston, TX, USA, to determine if there were systematic differences associated with socioeconomic status (SES). Patients of low SES reported higher scores on overall, information, and safety management (P<0.03) and no differences on medication, seizure, and lifestyle management. The two groups were similar with respect to the pattern of high and low scores. Reported levels of self-efficacy, depression, social support, stigma, desire for control, and outcome expectations were higher for those of high SES (P<0.01). Knowledge of epilepsy and satisfaction with care were lower (P<0.01). Again, the patterns of high and low scores were similar. Tests of association between psychosocial factors and self-management revealed that people with higher levels of self-efficacy and social support also reported higher self-management (P<0.01) regardless of demographics, seizure frequency, and SES (P<0.05). These findings provide little support for SES-related disparities in self-management and suggest that the focus of strategies to improve self-management may be similar across diverse populations.

Sociodemographic disparities in epilepsy care: Results from the Houston/New York City health care use and outcomes study.

PURPOSE: The purpose of this study was to identify sociodemographic disparities in health care use among epilepsy patients receiving care at different sites and the extent to which the disparities persisted after adjusting for patient characteristics and site of care. METHODS: Three months of health care use data were obtained from baseline interviews of approximately 560 patients at four sites. One-half of the patients were from a Houston site and two NYC sites that serve predominantly low-income, minority, publicly insured, or uninsured patients. The other half were at the remaining site in Houston that serves a more balanced racial/ethnic and higher sociodemographic population. Differences in general and specialist visits, hospital emergency room (ER) care, and hospitalizations were associated with race/ethnicity, income, and coverage. Logistic regression was used to assess the extent to which the differences persisted when adjusting for individual patient characteristics and site of care. RESULTS: Compared to whites, blacks and Hispanics had higher rates of generalist visits [odds ratio (OR) = 5.3 and 4.9, p < 0.05), ER care (OR = 3.1 and 2.9, p < 0.05) and hospitalizations (OR = 5.4 and 6.2, p < 0.05), and lower rates of specialist visits (OR = 0.3 and 0.4, p < 0.05). A similar pattern was found related to patient income and coverage. The magnitude and significance of the disparities persisted when adjusting for individual characteristics but decreased substantially or were eliminated when site of care was added to the model. DISCUSSION: There are sociodemographic disparities in health care for people with epilepsy that are largely explained by differences in where patients receive care.

Quality improvement: stroke plan-do-study-act for primary stroke center certification.

The 10-year aftermath of Shortell and colleagues' landmark intensive care unit study has resulted in healthcare institutions increasingly strategizing themselves into disease-specific niches. Specialization has evolved to the point at which The Joint Commission will certify exceptional disease programs. One such certification has been developed for stroke. The processes essential to attain stroke certification are detailed, complex, and outlined in this article.

Zonisamide monotherapy in a multi-group clinic.

OBJECTIVE: Reports on zonisamide monotherapy are limited despite favourable preliminary data, and typically restricted to tertiary referral centres. The goal of this study is to report clinical experience with zonisamide monotherapy in a large, multi-group clinic setting. METHODS: We reviewed the charts of patients treated with zonisamide monotherapy in the Neurology Department of the Kelsey-Seybold Clinic (Houston, Texas) during an 18-month period. We analysed subgroups of patients who were naive to antiepileptic drug (AED) therapy (Group 1) and those who had previous exposure to AEDs (Group 2). RESULTS: The study included 54 paediatric and adult patients with a variety of seizure types: 15 patients in Group 1 and 39 patients in Group 2. Mean maintenance zonisamide dosages in the two groups were similar (193 mg/day in Group 1 vs. 218 mg/day in Group 2). Thirty-eight patients (70.4%) continued zonisamide monotherapy, with 7 patients (13.0%) adding a second AED and 9 patients (16.7%) switching to a different drug. Of the 24 patients who became seizure free on zonisamide monotherapy, 11 were on the 100-mg initial dosage. Zonisamide monotherapy was well tolerated. CONCLUSIONS: Zonisamide monotherapy is safe and effective for a variety of seizure types and may be appropriate as first-line therapy in some cases.