Parkinson’s disease is a neurodegenerative disorder characterized by the accumulation of intracellular aggregates of misfolded alpha-synuclein along the cerebral axis. Several studies report the association between intestinal dysbiosis and Parkinson’s disease, although a cause-effect relationship remains to be established. Herein, the gut microbiota composition of 64 Italian patients with Parkinson’s disease and 51 controls was determined using a next-generation sequencing approach. A real metagenomics shape based on gas chromatography-mass spectrometry was also investigated. The most significant changes within the Parkinson’s disease group highlighted a reduction in bacterial taxa, which are linked to anti-inflammatory/neuroprotective effects, particularly in the Lachnospiraceae family and key members, such as Butyrivibrio, Pseudobutyrivibrio, Coprococcus, and Blautia. The direct evaluation of fecal metabolites revealed changes in several classes of metabolites. Changes were seen in lipids (linoleic acid, oleic acid, succinic acid, and sebacic acid), vitamins (pantothenic acid and nicotinic acid), amino acids (isoleucine, leucine, phenylalanine, glutamic acid, and pyroglutamic acid) and other organic compounds (cadaverine, ethanolamine, and hydroxy propionic acid). Most modified metabolites strongly correlated with the abundance of members belonging to the Lachnospiraceae family, suggesting that these gut bacteria correlate with altered metabolism rates in Parkinson’s disease. IMPORTANCE To our knowledge, this is one of the few studies thus far that correlates the composition of the gut microbiota with the direct analysis of fecal metabolites in patients with Parkinson’s disease. Overall, our data highlight microbiota modifications correlated with numerous fecal metabolites. This suggests that Parkinson’s disease is associated with gut dysregulation that involves a synergistic relationship between gut microbes and several bacterial metabolites favoring altered homeostasis. Interestingly, a reduction of short-chain fatty acid (SCFA)-producing bacteria influenced the shape of the metabolomics profile, affecting several metabolites with potential protective effects in the Parkinson group. On the other hand, the extensive impact that intestinal dysbiosis has at the level of numerous metabolic pathways could encourage the identification of specific biomarkers for the diagnosis and treatment of Parkinson’s disease, also in light of the effect that specific drugs have on the composition of the intestinal microbiota.

The objectives of this study were to evaluate the risk of neuropathy in patients with Parkinson's disease (PD) (P = 0.022; OR, 2.38; 95% CI,. In a comparison between patients with and without neuropathy (Student's ttest), the levodopa dose was higher (P < 0.0001), serum vitamin B12 levels were lower (P = 0.0102), and homocysteine levels were higher (P < 0.001) Parkinson's disease (PD) is a common neurodegenerative disorder that can cause significant disability and decreases quality of life. The cardinal physical signs of the disease are distal resting

Stichting ParkinsonFonds, Dorpmans-Wigmans Stichting, Erasmus Medical Center, ZonMw-Memorabel programme, EU Joint Programme Neurodegenerative Disease Research (JPND), Parkinson's UK, Avtal om Läkarutbildning och Forskning (ALF) and Parkinsonfonden (Sweden), Lijf and Leven foundation, and cross-border grant of Alzheimer Netherlands-Ligue Européene Contre la Maladie d'Alzheimer (LECMA).

Acknowledgments: this is a not-for-profit study. We thank Jane Tricker and Silvia Caviglia for editorial assistance in the preparation of this article. We are also grateful to Alessandra Rosa for assistance with the statistical analysis. This trial was partially supported by E.O. Ospedali Galliera Scientific Committee and Fondazione CARIGE. Manuscript received on February 24, 2011. Revised version arrived on June 30, 2011. Manuscript accepted on July 4, 2011. Email: gianluca.forni@galliera.it Deferiprone was shown to reverse iron deposition in Friedreich's ataxia. This multi-center, unblinded, single-arm pilot study evaluated safety and efficacy of deferiprone for reducing cerebral iron accumulation in neurodegeneration with brain iron accumulation. Four patients with genetically-confirmed pantothenate kinase-associated neurodegeneration, and 2 with parkinsonism and focal dystonia, but inconclusive genetic tests, received 15 mg/kg deferiprone bid. Magnetic resonance imaging and neurological examinations were conducted at baseline, six and 12 months. Chelation treatment caused no apparent hematologic or neurological side effects. Magnetic resonance imaging revealed decreased iron accumulation in the globus pallidus of 2 patients (one with pantothenate kinase-associated neurodegeneration). Clinical rating scales and blinded video rating evaluations documented mild-to-moderate motor improvement in 3 patients (2 with pantothenate kinaseassociated neurodegeneration). These results underline the safety and tolerability of deferiprone, and suggest that chelating treatment might be effective in improving neurological manifestations associated with iron accumulation. Haematologica 2011;96(11):1708-1711. doi:10.3324/haematol.2011 This is an open-access paper. ABSTRACTly, agranulocytosis), currently represents the only possibility for removing and/or preventing iron accumulation in the brain. This was a multi-center, unblinded, single-arm pilot study, lasting one year, to evaluate the efficacy and safety of chelation therapy with deferiprone on cerebral iron accumulation in patients with a clinical diagnosis of NBIA. 4 Design and Methods PatientsInclusion criteria were: patients over 18 years of age with neurological symptoms correlated with iron deposition in the basal ganglia as documented by MRI (T2* and T2 signal decrease in the basal ganglia), performed within six months of enrolment. Exclusion criteria were: inability to undergo MRI; renal insufficiency (creatinine >1.5 mg/dL); neoplasias, systemic cardiovascular, severe renal and hepatic diseases; known hypersensitivity to deferiprone; pregnancy and breastfeeding. Additional exclusion criteria were average alanine transaminase (ALT) levels over 300, variations in ALT or aspartate transaminase (AST) levels of 300% during the year prior to enrolment, and patients judged potentially unreliable and/or uncooperative with regard to study procedures.The trial was approved by the E.O. Ospedali Galliera Ethics Committee and the local Ethics Committee at the Cagliari cent...

Background-Data on long-term risk and predictors of recurrent thrombotic events after ischemic stroke at a young age are limited. Methods and Results-We followed 1867 patients with first-ever ischemic stroke who were 18 to 45 years of age (mean age, 36.8±7.1 years; women, 49.0%), as part of the Italian Project on Stroke in Young Adults (IPSYS). Median follow-up was 40 months (25th to 75th percentile, 53). The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. One hundred sixty-three patients had recurrent thrombotic events (average rate, 2.26 per 100 person-years at risk). At 10 years, cumulative risk was 14.7% (95% confidence interval, 12.2%-17.9%) for primary end point, 14.0% (95% confidence interval, 11.4%-17.1%) for brain ischemia, and 0.7% (95% confidence interval, 0.4%-1.3%) for myocardial infarction or other arterial events. Familial history of stroke, migraine with aura, circulating antiphospholipid antibodies, discontinuation of antiplatelet and antihypertensive medications, and any increase of 1 traditional vascular risk factor were independent predictors of the composite end point in multivariable Cox proportional hazards analysis. A point-scoring system for each variable was generated by their β-coefficients, and a predictive score (IPSYS score) was calculated as the sum of the weighted scores. The area under the receiver operating characteristic curve of the 0-to 5-year score was 0.66 (95% confidence interval, 0.61-0.71; mean, 10-fold internally cross-validated area under the receiver operating characteristic curve, 0.65).© 2014 American Heart Association, Inc. 1 Although it is well documented that such a risk is much lower in young patients with stroke than in elderly patients, information on what specific factors may predict recurrent events in younger age groups are limited. Most data derive from single-center studies enrolling several hundred patients or less, 2 using different thresholds of age to define young, and sometimes being biased by the inadequate capture of cases, the inclusion of different ethnic groups, and the high number of patients lost to follow-up.3 This makes such studies somewhat heterogeneous and their findings poorly comparable. In addition, the influential effect of some specific factors is missing in most previous studies. This is the case, for example, of patients' adherence to secondary prevention therapies, which is likely to impact the recurrence of potentially avoidable vascular events. The Italian Project on Stroke in Young Adults (IPSYS) provides the opportunity to investigate these issues owing to its large sample size, the homogeneous demographic characteristics and clinical phenotype of the subjects included, and the standard diagnostic workup. Therefore, in the present study we aimed at (1) elucidating the predictors of long-term recurrent vascular events after first-ever IS, and the extent to which these factors can be modified, which implicates the potential of reducing this risk,...